Triosephosphate isomerase (TPI, EC is essential to glycolysis, catalyzes the fifth step in the glycolysis pathway the reversible conversion of dihydroxyacetone phosphate (DHAP) into glyceraldehyde-3-phosphate. TPI is a homodimer formed by two identical dimeric molecules of a single structural locus : 12p13.31. TPI has only 1 functional gene with a molecular mass of 29 kDa, that after refinement are products of a distinct single structural locus. The variant phenotype of identical subunits are expressed in both red cells and circulating lymphocytes, catalyzing the interconversion of one of the two products breakdown by reversible conversion. The TPI substrate by deprotonation the transition state reaction of dihydroxyacetone phosphate (DHAP) substrate yields one product of the glycolytic pathway, is a trend* (Kcat) that persists creating the initial complex microcompartmentation of TPI to give (G3P) glyceraldehyde-3-phosphate which seems to be the isomerase* activity, release is slower than its conversion to DHAP in normal and TPI deficient cells. TIM with its natural substrates has not been () crystalized**. TPI is a dimeric enzyme and contains 7 exons interrupted by six introns.

monomers The crystallographic structure of (HsTPI) human triosephosphate isomerase PDB:1HTI is one dimer per asymmetric unit subunit 1 and subunit 2 are in the open and closed conformations in the 3-dimensional asymmetric space group P 2(1) which is specific to the Monoclinic with minimization on the entire structure in the presence of substrate analogues and its surrounding residues supporting possible regions targeted for drug design.
TPI deficiency (TPID) a disorder of glycolysis, occurring in haplotypes of specific alleles heterogeneous to clinical TPIdeficiency, with a rare homozygous deficiency the resulting genetic defect is the cause of a null variant incompatible with life by abnormally high levels of DHAP which degrades spontaneously into the toxic (MG) methylglyoxal, due to deamidation of asparagine (Asn15-71) to form aspartic and glutamic acid. Loop 6 plays a role in preventing the breakdown yield of methylglyoxal (fMG) one of the of the three products of enzyme-bound enediol(ate) phosphate, towards elimination of (fMG) inorganic phosphate. TPI deficiency is due to the common aberrant dimerization (or the dissociation into inactive monomers) of mutation TPI 1591C, encoding a Glu104-to-Asp (glutamate-to-aspartate) substitution in the TPI variant found in cases of hemolytic anemia coupled with neurodegeneration, the Glu104-to-Asp substitution is the most common disease allele inherited, when compared to wild-type TPI’s three (residues from the same subunit) similar but not identical interactions between the inhibitor and catalytic residues, Glu 167 (or 165) forms a stable dimer and provides the rationale for production of structurally normal enzyme in humans, the E104D mutation, provides the amyloid-resistant structure of human triosephosphate isomerase (HsTPI). Water-protein molecules join two catalytically active monomers which is only in its dimeric form, as monomers of TIM are not functional. Within a hydrophobic catalytic pocket of the native enzymes the binding and catalysis of TPIs in hemolysates, bind to the red cell membrane. Molecular modeling using the human crystal structure of TPI was performed to determine how these mutations could affect enzyme structure and function. The Amyloid secondary structure autoepitopes antigen-driven mechanism works toward recovery of the anti-triosephosphate isomerase mutant TPI peptide** antigens. This is the scheme that allows function-enhancing stability most significantly, the catalysis for deprotonation of DHAP or vice-versa GAP substrates of the TIM-barrel relative to TPI toward turnover of two-part substrate glycolaldehyde / phosphite dianion {GA + HPO32* the transition state for this enolising enzyme substrate pieces.} Km/obsd* group of the whole GAP substrate and H95 (loop 4) is also optimal for small mutational changes in or reflects its compatibility with amino acid residues which stabilizes the enediolate intermediate (GA/HPO) activity from change in the products scheme (a proton transfer mechanism) DHAP/G3P or interconversion of these intermediates.


Closed (activated for catalysis) of optimal WT (TPI) molecular modeling PDB 1HTI_B using the human crystal structure of TPI human triosephosphate isomerase (HsTPI) conformation 1hti_b, calculated to the incidence residue Water-protein molecules and the protein cage that interacts within a hydrophobic catalytic pocket isolated and examined which coded for human triose-phosphate isomerase. [EC:]….

TPI deficiency (TPID) a disorder of glycolysis, occurring in haplotypes of specific alleles heterogeneous to clinical TPIdeficiency, with a rare homozygous deficiency the resulting genetic defect is the cause of a null variant incompatible with life by abnormally high levels of DHAP which degrades spontaneously into the toxic (MG) methylglyoxal, due to deamidation of asparagine (Asn15-71) to form aspartic and glutamic acid. Loop 6 plays a role in preventing the breakdown yield of methylglyoxal (fMG) one of the of the three products of enzyme-bound enediol(ate) phosphate, towards elimination of (fMG) inorganic phosphate. TPI deficiency is due to the common aberrant dimerization (or the dissociation into inactive monomers) of mutation TPI 1591C, encoding a Glu104-to-Asp (glutamate-to-aspartate) substitution in the TPI variant found in cases of hemolytic anemia coupled with neurodegeneration, the Glu104-to-Asp substitution is the most common disease allele inherited, when compared to wild-type TPI’s three (residues from the same subunit) similar but not identical interactions between the inhibitor and catalytic residues, Glu 167 (or 165) forms a stable dimer and provides the rationale for production of structurally normal enzyme in humans, the E104D mutation, provides the amyloid-resistant structure of human triosephosphate isomerase (HsTPI). Water-protein molecules join two catalytically active monomers which is only in its dimeric form, as monomers of TIM are not functional. Within a hydrophobic catalytic pocket of the native enzymes the binding and catalysis of TPIs in hemolysates, bind to the red cell membrane. Molecular modeling using the human crystal structure of TPI was performed to determine how these mutations could affect enzyme structure and function. The Amyloid secondary structure autoepitopes antigen-driven mechanism works toward recovery of the anti-triosephosphate isomerase mutant TPI peptide** antigens. This is the scheme that allows function-enhancing stability most significantly, the catalysis for deprotonation of DHAP or vice-versa GAP substrates of the TIM-barrel relative to TPI toward turnover of two-part substrate glycolaldehyde / phosphite dianion {GA + HPO32* the transition state for this enolising enzyme substrate pieces.} Km/obsd* group of the whole GAP substrate and H95 (loop 4) is also optimal for small mutational changes in or reflects its compatibility with amino acid residues which stabilizes the enediolate intermediate (GA/HPO) activity from change in the products scheme (a proton transfer mechanism) DHAP/G3P or interconversion of these intermediates.


Structure of human triose phosphate isomerase at the positions of introns in homologous TPI genes from a number of phylogenetically diverse species. The introns motif are identified as calculated in phylogeny.
Phylogenetic trees constructed on the basis of sequence comparisons for triosephosphate isomerases analysis, TIM sequences were constructed based phylogeny with similarity, to those adopting the same structural fold of interest from different species for the taxonomic groups and the K13M mutations involvement in the human triosephosphate isomerase gene family
Interactions in the loop regions combine the effects of His95 and Lys13 for Glu165 (loop 4, 1, and 6) the three crucial catalytic residues in triose phosphate isomerase, all form the enediol intermediate necessary for the interconversion reaction catalyzed by TIM resulting in the natural substrates G3P formation. The introns motif are identified as calculated in phylogenic motifs. Poorly conserved residues as targets for specific•• drug design are expected when compared to (TPI) Triosephosphate isomerase (•). Catalytic residues of the phylogenetic relationship pathways obtained by sequence based methods of specific key amino acids can than be calculated to the incidence residues and other TIMs which may influence the (human) HsTPI equilibrium.

Non-Phosphorylating And Phosphorylating Oxidoreductase Glyceraldehyde-3-Phosphate Dehydrogenase As Part Of A Structure-Based Design In Glycolysis As The Glycolytic Protein G3PD.

Glyceraldehyde-3-phosphate dehydrogenase (EC GAPDH1/G3PD, is located in band 12p13.31; related to both glycolysis2 and gluconeogenesis-pathways. G3PD catalyzes reversible oxidative phosphorylation of inorganic phosphate and nicotinamide3 adenine dinucleotide (NAD)4 converting in glycolysis the glycolytic protein GAPDH5 in which adenosine-triphosphate (ATP)6 is generated when phosphoglycerate kinase (PGK)7 is produced in the GAPDH8-catalyzed reaction. These intermediate metabolites (aldolase9, triose-phosphate10-isomerase (TPI)11) catalyze the Glycolysis reactions, in the sequence of the ten enzyme-catalyzed Embden12Meyerhof13 reactions in the metabolic pathway. Converting phosphoglycerate mutase 1 (PGM)14 catalyzing the internal steps by 2,3-BPG15 phosphatase to form by converting D-glyceraldehyde 3-phosphate (G3P)16 into 1,3-bisphosphoglycerate (1,3-BPG)17 from its role as 3-Phosphoglyceric acid (3PG) in glycolysis as the glycolytic protein GAPDH18 that catalyzes the first step (G3P19 into 1,3-BPG) of the pathway. Plant20 cells contain several reactions of photosynthesis21 participating in glycolysis and the Calvin-Benson22 cycle signaling pathways in plants (cytosolic-GAPC23 (Arabidopsis thaliana)24 functions in plant25 cells.) its final byproduct is also another Glyceraldehyde-3-P. GAPDH is a band 326 protein that associates with the cytoplasmic27 face of human erythrocyte28 (RBC)29 membranes. The cytoplasmic GAPDH exists primarily as a tetrameric30 isoform, 4 identical 37 kDa31 subunits. By subcellular translocation GAPDH32 participates in nuclear events [In nuclear membrane the vesicular33 tubular cluster fractions34 (VTCs)35 – anterograde transport or retrograde36 membrane transport complexes37 between the intermediates, these are the Golgi38 complex and the endoplasmic reticulum (ER)39, in the nucleus a function is lost in disease that exploits this process.], this a change to a non-cytosolic40 localization due to the signal transduction pathways (considering Lm41GAPG L.42 mexicana43-like functions.) involved in s-nitrosylase44 activity that mediates, governed by the equilibrium between four cysteine residues (nitrosylation45 and denitrosylation reactions)46, inhibition of GAPDH nuclear translocation, as a basis47 for its multifunctional48 activities relating to the extraglycolytic functions of GAPDH. Nuclear GAPDH49 promotes glucose metabolism to sustain50 cellular ATP51 levels, or potentially by inhibiting targets52 of p30053/CBP such as p5354 dependent phosphorylation. Nitric oxide synthase or neuronal NOS ( involved in cellular and human intracellular55 nuclei events56, in addition to the cytoplasm) could generate nitric oxide57 (NO). GAPDH has four cysteine58 residues which are associated with S-nitrosylation59-yielding NOS60-GAPDH which “recruited” its glycolysis subunit61 from the three63 molecular axes translocation roles (S-thiolation64, S-nitrosylation or aggregated65 enzymes (Cys-15266 and nearby 15667 converted into a ‘cross-linked68 soluble’ states)), and (SNO69-GAPDH) nitrosylated S-nitrosoglutathione70 (GSNO)71 the active site cysteine residue in GAPDH at its Cys 15072 residue that binds to Siah1 (seven in absentia homolog 1) acquisition and the translocation of GAPDH into the nucleus, and denitrosylation using a combination of approaches, including G3P73 . And NADPH may play a role in (VTC) vesicle74 function. The complex would function in the apoptosis cascade75 by its molecules translocation, this may76 depend on lysine 22777 in the human GAPDH78Siah79 interaction to another intracellular position80 induced by apoptotic81 stimuli, augments p30082/CREB binding protein (CBP)-associated83 acetylation of nuclear proteins. ‘Engineering the cofactor (GAPDH-(Lys) K160R84-K227A) availability prevents85 activation of p300/CBP that interferes with GAPDH-Siah1 binding86-prevents the ternary (GAPDH-Siah1) complex associations translocation; that CGP-346687 can reduce independently with both cofactors88. Dysregulation of protein S-nitrosylation (S-nitrosocysteine89247) by lipopolysaccharide (LPS) is associated with pathological90 conditions which contributes to disease phenotype, where GAPDH protects ribosomal protein RP91L13a92 from degradation, L13a93 and GAPDH94 forms a functional GAIT95 complex. One of the functions of GAPDH proteins role in glycolysis96 in relation to DNA97 synthesis is nuclear accumulation associated by the NAD98(+)-dependent s-nitrosylation99 and denitrosylation01 reactions both of these isforms are distinct02 parallel to the uracil DNA glycosylase (UDG)03 gene in mitochondria04 and in the nucleus is N-terminally processed is the 37-kDa subunit05 of the (GAPDH)06 glyceraldehyde-3-phosphate dehydrogenase protein. This enzyme is an example of moonlighting protein which is validated and replaced07 by alternative reference genes that link (in their nuclear forms) on the multifunctional08 properties of the enzyme GAPDH09 known as a key enzyme in glycolysis that contributes to a number of diverse cellular functions unrelated00 to glycolysis001 depending upon its subcellular location. GAPDH is a key enzyme in glycolysis the most commonly used expression is as a housekeeping002 gene.

Cytotoxic stimuli [1a.] or Programmed cell death, via nitric oxide generation, lead to the binding of GAPDH from its usual tetrameric form to a dimeric form, to the protein Siah1 [1.] intracellular G-3-P [2.] substrate [3.] protects GAPDH from S-nitrosylation [4.]. The GAPDH-Siah interaction depends on lysine 227 [5.], in human GAPDH that interacts with a large groove [6.] of the Siah1 dimer, that connects the GAPDH dimer to PGK in the cytoplasm. figure7The S-nitrosylation [7.,8.] abolishes catalytic activity and confers upon GAPDH the ability to bind to Siah [9.]. (GAPDH) is physiologically nitrosylated at its Cys 150 residue. GAPDH (SNO-GAPDH) [10.] binds to Siah1 [11.] by forming a protein complex. In the nucleus [12.] GAPDH is acetylated at Lys 160 [13.] and binds to the protein acetyltransferase p300/CBP. Under these conditions siah-1 formed a complex with GAPDH (PDB:4O63) and localized in the nucleus of Müller cells [14.]. GAPDH mutants [15.] that cannot bind Siah1 prevents translocation [16.] to the nucleus to elicit neurotoxicity [17.] and cell apoptosis.

[1a.] 16492755, 8769851003 [1.]16391220, [2.]19542219, 22534308, 3350006004, 19937139, [3.]22847419, [4.]15951807, [5.]20601085, [6.]16510976, 20392205005, [7.,8.]22817468006, 16505364007, [9.]16633896, [10.]16574384, [11.]20972425, [12.]19607794, [13.]18552833, [14.]19940145, [15.]23027902008, [16.]24362262, [17.]16492755.

Analysis of CGP-3466 Docking (NAD) to Human Placental GAPDH which decreases the synthesis of pro-apoptotic proteins is N-terminally PMID:10677844, processed to which a Rossmann NAD(P) binding fold as seen in figure 1 is a C-terminal domain as seen on this page, PMID:10617673, 26022259, 16510976 …The structure is also used to build a model of the complex between GAPDH and the E3 ubiquitin ligase Siah1. (Purple Ribbon-1U8F_Q Figure 1.)

In the GAPDH-catalyzed reaction these intermediate metabolites (aldolase, triose-phosphate-isomerase Glycolysis and Glyconeogenesis (TPI)) catalyze the Glycolysis reactions, in the sequence of the ten enzyme-catalyzed Embden-Meyerhof reactions in the  metabolic pathway. Converting phosphoglycerate mutase 1 (PGM) catalyzing the internal steps by 2,3-BPG phosphatase to form by converting D-glyceraldehyde 3-phosphate g3p(G3P) into 1,3-bisphosphoglycerate (1,3-BPG) from its role as 3-Phosphoglyceric acid (3PG) in glycolysis as the glycolytic protein GAPDH that catalyzes the first step (G3P into 1,3-BPG) of the pathway.

GAPDH homotetramer was studied as represented an assembly of repeating spherical units that harbored a distinct birefringent crystal structure to the optic axis for the p polarization, also (r axis) discernible via transmission electron microscopy. of the relative amount of soluble monomeric GAPDH to G3P in the binding pocket of the NAD(+)-binding site residue located at the active site linked to GAPDH in Figures 5 and 6. PMID:10407144009, 25086035.

g3pAnother model building studie indicates that a structure obtained where glyceraldehyde 3-phosphate PDB:3CMC_Q binds in the P(s) pocket of the natural substrate G3P phosphorylating GAPDH (PDB:1U8F_Q) at the catalytic cysteine residue site. To define the conditions suitable for affinity for the cosubstrate, the isolation and accumulation of the intermediate metabolites per G3P monomer found in Figure 8 of the equivalent Glc-3-P structure in the binding pocket of the NAD(+)-binding site residue located at the active site linked to GAPDH. PMID:19542219, 22534308

Correctly known binding sites on ((GAPD/NAD)) structures, polar spheres of the binding catalytic pocket that corresponds to G3P (glyceraldehyde 3-phosphate) aligned to the holographical structure nonbounded spheres (salmon color), these apoenzymes together with the cofactor(s) Cys 151, 152 which corresponds as below the Ps pocket of G3P, on the Green ribbon required for cofactor activity. Together with eliminated crystallographic waters and other possible spheres, these are at least one atom of a amino acid residue in contact with at least one alpha sphere of one binding pocket on the holo protein NAD structure 1U8F_Q needed to align holo and apo structures included in this data set with G3P (PDB:3CMC_Q) was tested only on holo structure (NAD), obtained via Pea Green spheres aligned to 1U8F_Q ribbons/ligand structure which provide structural recognition insights into the biological 1U8F-Q assembly this includes 29 asymmetric units of its dimeric form, along the tetrameric 1U8F biological forms axis. PMID:9461340010

(Figure 8.) These are the results without the liquid chromatography coupled mass spectrometer, that are known 3D products by two-dimensional sequence analyses with the STRAP alignment tools data sets and which may have any effect on the functions of further analysis involved in more ordered results than this study attempts to show, of the analysis that may be included are identified separated into multiple gradients here in these paired graphs. Therefore in the present work to uncover the exact coincidence of 1U8F_R and 4I7D_C, the 3D coordinates of GAPDH (PDB:1U8F_Q) to the protein Siah1 4I7D were not presenting when subjected to STRAP  alignment this apparent discrepancy (Figure 1.) was partially resolved by a (Figure 7) rendering from a more reactive native GAPDH_R homotetramer model.


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Glutathione reductase (GSR, GR) locus in the chromosomal region 8p21.1, (EC§, ) is a protein-S-glutathionylation, as a (human) Mitochondrial localization of hGSR and its associated enzymes cellular thiol/disulfides S-Glutathione reductase (GSR) which is the importance of significance in reversible thiol modifications which  regenerates reduced glutathione (GSH) and GSSG to the reduced form found in the obvious structural properties of glutathione reductase. The redox regulating enzymes relationship with TTase (thioltransferase) activity with the ratio of the activities of G3PD, as the mechanism (of cellular repair) ‘differs’ (gssg-g6pg) according to the type of reducing glutathionylated mixed disulfide, including protein-S-S-glutathione (PSSG), GSR reduces (PSSG) modified by thiolation to a normal level in human lens epithelial (HLE) cells. This may have implications in stress- and aging-related pathologies in astrocytes and granule cells, demonstrated by comparable mitochondria/cytosolic concentrations of its thiol proteins, where a mitochondrial leader sequence (cDNA) is present in the gene structure of human GSR and may be the Cytoplasmic Isoform (derivative or inhibitor formed) of  mitochondrial dysfunction that contains the catalytic cysteine revealing a possible therapeutic strategy/target, also indicating transiently accumulated inhibitor proteins modified by thiolation (cysteine catalytic subunits) compounds that inhibit these (re)activation processes (hGSR) with its structure-based prosthetic group (FAD) cofactor is common because of the levels of cysteine available; are mitochondria/cytosolic concentrations that the Glutathione reductases reversible thiol modifications which catalyzes the reduction of GSSG to GSH the natural GR substrate is dependent on the NADPH:GS-SG ratio.
PDB Id: 3DK9 Cys58 and Cys63 represent the enzyme’s results seen as the reductive (GSH) Cys-58 and oxidative (GSSG) Cys-63 is the relationship of these two enzymes, His467‘ is seen to interact with Cys63 more optimally and Cys-58 produces the second GSH intermediate molecule of the reaction is the reduced glutathione-to-oxidized glutathione ratio (GSH/GS-SG) when compared to the substrate free form correlated with (FAD) the flavin compounds, flow from NADPH to the substrate GSSG via flavin. The reducing equivalents needed for regeneration of GSH are provided by NADPH. The enzyme has affinity for flavin adenine dinucleotide (FAD) the prosthetic group of GR, and maintains high levels of reduced glutathione  (Cytoplasmic Isoform: Produced by alternative initiation of isoform Mitochondrial homodimer, derivative or inhibitor formed from the GSR Pyridine, dimerisation domain.) in the cytosol. Glutathione reductase (GR) plays a key role in maintaining either a thiol group or a nonprotein sulfhydryl group (NPS) form of GSH, and potential for thioredoxin and glutathione systems, as thioredoxin dose not require GSH and GR for catalytic activity. Glutathione reductase (GR) utilizes NADPH produced by G6PDH (glucose-6-phosphate dehydrogenase) enzyme activities, and enzyme glutathione reductase (GR) represents the erythrocyte glutathione-reducing system (GRS), of the GSH pathway to oxidation and inactivation in the activity of GSH peroxidase and GSH reductase. Expression of the regulatory subunit of gamma-glutamylcysteine synthetase/ligase (GCL) catalyzes the first and rate-limiting step in the production of the cellular (GSH) glutathione. Dietary riboflavin (Vitamin B2) intake produces its active essential coenzyme flavin forms, riboflavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) of glutathione reductase (GR), or the GR activity correlated with red-cell flavin compounds.When both GSSG and NADP(+) substrates and products are present, glutathione reductase (GR) is a enzyme required for the conversion in the presence and absence of flavin adenine dinucleotide (FAD), glutathione reductase (GR) is an obligatory FAD-containing homodimer. GSSG via glutathione reductase (GR) regenerates reduced glutathione which is essential for antioxidant defense. The flavoenzyme glutathione reductase (GR) reduces ‘oxidized glutathione’ (GSSG) back to GSH, also involving glutamate-cysteine ligase and modulatory (GCL)-can be upregulated ∉ as the cellular GSH system, indicating short-term and heritable tolerance of exposure to oxidative stress from/via numerous reporting ∈ mechanisms. NADPH is used by glutathione reductase for the reduction of oxidized glutathione (glutathione disulphide) GSSG to GSH-dependent peroxide metabolism. 4-Hydroxynonenal (HNE) is one of the major end products of lipid peroxidation which may lead to enhanced action of  the (GSR) oxygen radical, glutathione S-transferases (GSTs) are specifically suited to the detoxification and removal of 4-HNE (∋ or ∝) from cells which may provide a basis for selective cellular and/or subcellular distribution of mitochondrial and cytosolic to individual detoxifying gene inducer activities of glutathione reductase (GR), the cellular (GSH) glutathione. It was evident the enzyme glutathione reductase (GR) represents the erythrocyte glutathione-reducing system (GRS), of the GSH pathway to oxidation and the (∉ or ∝) inhibition constant for reversible inactivation in the activity of glutathione related antioxidant enzymes. And GSH reductase may be one of the factors that remained in focus that suggests its effects on the antioxidant system related to glutathione synthesis (GCL), degradation, and functions.
Biological Xenobiotics, Extracts, Applications of note In the presence of Glutathione reductase.:
Schisandrin (Schisandra chinensis), used in traditional Chinese medicine. PMID:21328628
Transketolase (TK) and transaldolase (TA)
Melatonin PMID:15571523, 19475625
Blackberry (Rubus sp.) cultivars, The ‘Hull Thornless’,  PMID:11087537
Glutathione dehydrogenase (ascorbate)-[dehydroascorbate reductase (DHAR), and glutathione reductase (GR). This enzyme participates in the glutathione metabolism the active metabolite of vitamin D3 increases glutathione levels.] PMID:11087537, 23770363
3H-1,2-dithiole-3-thione nutraceutical D3T potently induces the cellular GSH system, Anethole trithione is a drug used in the treatment of dry mouth, the Anethole trithione isomer is related to anethole (anise camphor) used as a flavoring substance. PMID:17206382*, 19408115,     19176875*, 15896789, 18408143*, Glutathione reductase
Cassia fistula used in herbal medicine. PMID:19088944
Sanguinarine is extracted from some plants, including bloodroot and Mexican prickly poppy (Argemone mexicana) where argimone oil causes Epidemic dropsy. PMID:11260782
Vitamin E, PMID: 15672860
Tocotrienols are natural compounds members of the vitamin E family found in select vegetable oils are an essential nutrient for the body. PMID:21845802
Pyrrolizidine alkaloids are produced by plants as a defense mechanism against insect herbivores consumption of PAs is known as pyrrolizidine alkaloidosis. PMID:20144959
Apple extract (AE) PMID:20401791
Lipoic Acid an organic compound, forming a disulfide bond, available as a dietary supplement PMID:15246746, 21073761
Carnitine PMID:15246746, 10581232
Vitamin D upregulated expression of GCLC and GR. PMID:23770363
Vitamin D3_ PMID:12416023
Vitamin E_ PMID:10459841, 8360018, 18296478, 21845802, 15490422, 16885600, 7062348, 20729758, 21086752
Shidagonglao roots Mahonia fortunei (十大功劳 shi da gong lao) species contains the alkaloid berberine PMID:199382 18
Coenzyme Q10 (CoQ10) PMID:16621054
Trigonella foenum graecum seed powder (TSP) PMID:15026271
Boschniakia rossica, a ̱̱̱Traditional Chinese medicine. PMID:19352025
Aegle marmelos commonly known as bael is a species of tree. PMID:18830880
Scoparia dulcis A medicinal plant, dulcis. PMID:21905284
Fenugreek (Trigonella foenum-graecum)  is used as a herb. PMID:15026271
L-arginine (L-Arg) semiessential supplementation common natural amino acid. PMID:16038634
Hypericum perforatum (St. John’s Wort) PMID:18754092
Urtica dioica often called common nettle PMID:12834006
Usnea longissima, a medicinal lichen. PMID:16169175
Capparis decidua, a fruting tree also used in folk medicine and herbalism. PMID:22272107
Indole-3-carbinol found at relatively high levels in cruciferous vegetables such as broccoli
PMID:9512722, 14512388
Ascorbate Vitamin C. PMID:14512388
Sulforaphane It is obtained from cruciferous vegetables such as broccoli. PMID:12628444, 18607771*, 22303412
Andrographis paniculata, may shorten the duration and lessen the symptoms of common cold. PMID:11507728
Vitamin B-1 (thiamine) PMID:1132146, 10450194, 21308351*, 11514662*, 1270885
Vitamin B2 (riboflavin) PMID: 5822598, 5550591, 1201246, 5794396, 237845, 3677785, 3582603, 12194936, 2721660, 1261528, 5721130, 14608016, 4400882, 7883462, 844948, 7337797, 5881,12641409, 4393763, 3497609, 16883966…(№ 1244, OMIM.138300)
Vitamin B-6 (Pyridoxine) PMID:2721660, 3582603, 10450194, 15490422, 1270885, 7417521, 7337797, 7814235
Vitamin B9 (Folic acid)  PMID: 844947, 1270885
Aspartate transaminase (AST) or glutamic oxaloacetic transaminase (GOT) catalyzes the interconversion of aspartate an important enzyme in amino acid metabolism. PMID:1132146, 10450194, 1253408
β-Carotene is a strongly colored red-orange pigment abundant in plants and fruits. PMID:19957244
3-Hydroxykynurenine (3OHKyn) a metabolite of tryptophan. PMID:11273669
Ajoene ((E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), a garlic-derived natural compound. PMID:9986706 PDB: 1BWC
Propolis a product made by bees. PMID:19394397
Resveratrol produced naturally by several plants PMID:12797471
No CiTO relationships defined:

Brenneman, M. R.
Changes in glutathione and glutathione reductase
positioning glutathione-s-transferase as a function of cell concentration
with enzyme activities found to influence behavior. (2015).

Thioredoxin reductase: Selenotetrapeptide sequences with specificity for thioredoxin and glutathione systems

  Thioredoxin reductase (EC TXNRD1 (Alternate Symbols: GRIM-12, TR, TRXR) chromosomal position 12q23.3-q24.1 (§, ) is a homodimeric selenocysteine-containing enzyme. Secys a selenocysteine residue is an essential TR isozyme component, located near the C-terminus region [cysteine (Cys)-497,Secys-498] of the intracellular, redox cellular environments center in the catalytically active enzyme site, Gly-499 is the actual C-terminal amino acid. In their N-terminal sequences Cys-59, Cys-64 links the thiol/disulfide oxidoreductase dependent pathway reductases from there to the flexible C-terminal part (Secys) of the other sub cellular subunit by which Selenocystine is efficiently reduced and induce RNR (Ribonucleotide reductase) for replication and repair, where Trx reductase (TR) or oxidized GSH (GSSG) reductase further supply electrons for RNR. The protein reversibly modulates specific signal transduction cascades, to regulate multiple downstream intracellular redox-sensitive proteins that links NADPH and thiol-dependent processes which catalyzes NADPH-dependent reduction in the presence of the redox protein-Trx and thioredoxin reductase (TR) maintain cysteine residues in numerous proteins in the reduced state. There are three TXNRD selenoproteins  5-prime end variants essential for mammals, one V3 (TXNRD1) encodes an N-terminal glutaredoxin (GRX) these variants code for thioredoxin glutathione reductases (TGR). V3 associates with and triggers formation of Filopodia (cytoplasmic filaments) can guide actin in migrating cells, the emerging protrusions of cell membrane restructuring involved is in ‘deglutathionylation values” for mitochondrial and cytosolic thioredoxin reductase (TR) domains. Characterization of the TR native Thioredoxin and glutathione systems (TGR) suggests that the lifecycle of E. granulosus and Schistosoma mansoni a phylum of Platyhelmintha, involves the TXNRD1_v3 isoform containing a fused (Grx) glutaredoxin domain which is abolished by deglutathionylation’ targeted to either mitochondria or the nucleus in the reduction of glutathionylated substrates, in leishmaniasis (disease) glutathione reductase system (TGR) is replaced by the trypanothione reductase (TcTR) system in mammalian cells, essential as these TR3 are significant as a recognized drug target of these (TcTR) human protozoan parasites. Cytosolic TR1, mitochondrialTR3 and TrxR2 (locus 22q11.21) where TrxR1 and TrxR2 are consdered as the respective cytosolic 1w1e MITOCHONDRIAL cytoplasmicand mitochondrial thioredoxin reductases, plus the thioredoxin glutathione reductases-TGR systems most likely can reduce (Trx) by fusion of the TR and an N-terminal glutaredoxin domains. As a pyridine nucleotide disulfide oxidoreductase of the oxidized GSH and GSSG (selenodiglutathione) reductase TGR structures enzyme stability, are linked to the previously characterized two thioredoxin reductases cytosolic TR1 and TR3, and one mitochondrial variant. Selenols are key metabolites at mammalian TXNRD1’s active (SeCys 498) site. Thioredoxin undergoes NADPH-dependent reduction (NTRs) and reduce oxidized cysteine groups on mitochondrial TXNRD1 proteins similar to the cytosolic enzyme, from the FAD binding domain where the active cystines and the NADPH binding domain are contained, plus an interface domain (ID) of the C-terminal interface homologous to glutathione reductase identifies a mechanism of p53 mediated cell death regulation involving (TrxR) enzymes of redox homeostasis reactions to overcome the oxidative stress generating reactive oxygen species (ROS) on a complex combination of decreased apoptosis to prevent permanent cell damage and cell death that tumor cells use to evade the redox-sensitive signaling factors, or resistance to therapy. End products of lipid-peroxidation, 4-HNE-(4-Hydroxynonenal) can induce oxidative stress, other isoforms are more water-soluble adducts detoxifying such a buildup,  peroxidation might be limiting their (selenoproteins) proper expression. Thioredoxin reductase (TrxR) is the homodimeric flavoenzyme that catalyzes reduction of thioredoxin disulfide (Trx) one of the major redox control systems, involving a second interaction between NAD(P)H and/or (quinone reductase) NQO1 via the FAD-containing enzyme (TR), thioredoxin reductase forms an oxidoreductase system. TrxRs are able to reduce a number of substrate proteins other than Trx.

3qfbThe 3′ UTR of selenocysteine-containing genes have a common stem-loop structure, the sec insertion sequence (selenocystine-SECIS, PDB: 2ZZ0), that is necessary for the recognition of a catalytically active Sec codon rather in the values for mitochondrial and cytosolic thioredoxins reductase (TR) domains. The Sec residue is protonated at a different pka than in comparison to that of Cysteine. Cys59-Cys64 two cysteines pair also was oxidized in the N-terminal FAD domain essential for thioredoxin-reducing activity, and the need for Sec-498 (PDB: 2J3N) to be in complex with the FAD and NADP(+) during catalysis to the N-terminal active site cysteine residues Cys59-Cys64 and from there to the C-terminal part of the other subunit which have selenotetrapeptide sequences from the other module (PDB: 2J3N). Secys498 forms, (Human PDB 3QFB,) can both be identified at active site of the enzyme Gly-499 of the subunits active Cys-497-TRXR1 (the TR1 structure PDB: 3QFB) are the mechanism(s) for the incorporation of Se into TrxRs as the amino acid selenocysteine (Sec), as well as for delivery to a variety of secondary substrates or TRX (PDB: 3QFB) in nuclei provide means to quantify glutathione (GSH) (PDB: 3H8Q) conditions of the active GRX functonally and structurally analogus to TGR (selenodiglutathione) reductase. These two were modeled parts of TGR were linked to V3 (_TXNRD1) encodes an N-terminal inter-specific glutaredoxin (PDB: 1JHB).3qfb-3h8q From the FAD binding domain-(PDB: 1ZKQ ) active cystines and the NADPH binding domain where they are contained, plus an interface domain (ID) of the C-terminal ID in complex with its substrate thioredoxin (Trx-PDB: 1TRX, TXNRD1-3QFB) bringing Cys32 in Trx1 close to Cys497 in 3H8Q to quantify glutathione (GSH) that helped in characterizing  what was separately modeled as the Thioredoxin reductase (TXNRD1) domain which are consdered as the respective cytosolic and mitochondrial thioredoxin reductases units with a model obeying standard geometry that is conceivable of human thioredoxin reductase 1-2 and 3’s structures glutaredoxin domain 3H8Q  in complex with the FAD and NADP(H) when replaced by the TcTR (PDB: 2W0H) trypanothione/trypanothione reductase system involves a phylum of Platyhelmintha, where a glutathione (GSH) isoform containing a fused (Grx) glutaredoxin domain  (PDB: 1JHB) is essential for the parasite survival.  The intricate substrate specificities for the thioredoxin (Trx) system which consists of native Trx and the respective cytosolic  mitochondrial thioredoxin reductase (TrxR) enzymes are likely to be of central importance to these observations as a determinant of TrxR function in general, each (the thioredoxin reductase/thioredoxin pathway) can reduce a number of different types of substrates or cross-reactive-bound enzyme fractions as active with thioredoxin.
[1.] Selenium yeast: seleno yeast PMID: 16857846
[2.] Sulforaphane From Broccoli PMID: 16377050, 12742546, 20204301, 12949356, 19595745, 17150329, 15740016, 12663510, 15998110, 17300148
[3.] Chlorella vulgaris: corresponding to a chloroplast NADPH-dependent thioredoxin reductase gene (NTR-C), in Chlorella PMID: 18029787
[4.] Scutellarin:  It can be found in Scutellaria barbata and S. lateriflora. PMID: 15131321
[5.] Curcumin (TURMERIC plant of the ginger family): PMID: 21782934, 20160040, ~15879598
[6.] Experiments in E. huxleyi genus phytoplankton PMID: 20032866
[7.] Gambogic Acid pigment of gambooge resin from tree species Garcinia gummi-gutta. PMID: 24407164
[8.] Shikonin an antioxidant (no longer approved for use,: targets the Sec residue [13.] in TrxR1 to inhibit its physiological function. see: (Methane-) methylseleninic acid (MSA)) obtained from the extracts of  plant [9.] Lithospermum erythrorhizon. PMID: 24583460
[10.] Black tea extract (BTE) theaflavin (TF) PMID: 19059456
[11.] Green tea extract-epigallocatechin-3-gallate (EGCG) PMID: 19020731
[12.] Eicosatetraenoic acid, (Mortierella Alpina Oil) Arachidonic acid (AA) all-cis-5,8,11,14-eicosatetraenoic acid, 5-Hydroxyicosatetraenoic_acid_and_5-oxo-eicosatetraenoic_acid PMID: 15123685
[13.] Juglone: In the food industry known as C.I. Natural Brown 7 and C.I. 75500. (DTNB assay, a synthetic approach for Cys and Sec residues.) PMID: 21172426, 11170645, 18382651 … a 5,5′-[dithiobis Pyritinol: analogue, Sulbutiamine]
[14.] The antioxidant ubiquinol-10 (Q10) PMID: 12435734
[15.] Rottlerin, conductance potassium channel (BKCa++) opener, source the Kamala tree. PMID: 17581112
[16.] Ajoene a chemical compound available from garlic. PMID: 9986706
No CiTO relationships defined

Catalase, the antioxidant heme enzyme one of three subgroups related to catalase deficiency in humans modulating the normal catalase reaction dependent on NADPH-binding catalases for function.

Catalase (CAT) is converted by decomposition and intracellular localization relationships of the main cellular antioxidant enzyme system like superoxide dismutase (SOD), peroxiredoxins (Prdx), and glutathione peroxidase (GPX) are peroxisomal matrix enzymes in the cytoplasm, translocated to the peroxisomes to catalyze hydrogen peroxide H2O2 which is decomposed to oxygen and water, locus: 11p13 (§, ). Unlike catalase, the objective of this communication, SOD which prevents the formation of Hydroxyl radicals – (HRGT) determined from constant of O2.- dismutation, and generation of reversibly inactive (CAT)-compound II, Panax ginseng could induce both transcription factors. Catalase is  composed of four identical subunits each of the subunits binds one heme-containing active site, and produces two catalase compounds HPI and HPII (PDB: 1p80) is flipped 180 degrees » with respect to the orientation of the heme related to the « root mean square to the structure of catalase, (Mutation Location) from peroxisomal catalases inactive state in compound II NADP+(H) binding pockets inverted remains similar to the structure of the wild type (Val111, PDB:1A4E, KatG) orientation on the heme proximal (PDB: 1GGK) side, inactivate catalase can be prevented by melatonin. Catalase (CAT; EC a  free radical scavenging enzyme (FRSE) is a scavenger of H2O2. Protoporphyrin – (ZnPPIX) (PDB: 1H6N), from a heme group of the ‘heme-pathway, which forms catalase,’ is a scavenger of antioxidant (HO-1-HMOX1) heme oxygenase, involving ROS. Catalase is part of the enzymatic defense system constituting the primary defense against ROS, zinc protoporphyrin IX (ZnPPIX) is an inhibitor of (HO-1) heme oxygenase. Catalase protects the cell from oxidative damage by the accumulation of cellular reactive oxygen species (ROS) generation systems, those peroxisomal enzymes that breaks down hydrogen peroxide after H(2)O(2) exposure, and thereby mitigates* (some contradictory* results) the toxic effects of hydrogen peroxide. In the process (The typical hydroperoxidases (CAT) known as Compound I) of the substrate of catalase, NADP+ (an inactive state, compound II) is replaced by another molecule of NADP(H) to provide protection of catalase against inactivation by (H2O2) hydrogen peroxide. Erythrocyte  [Human erythrocyte catalase (HEC), The NADPH-binding sites were empty – PDB: 1F4J, 1QQW] and plasma indices (enzymatic-antioxidants) initially implies the thiobarbituric acid-reacting substances (TBARS) based on reaction with hydroxyl radicals (OH) can release thiobarbituric acid, TBAR inhibition measures malondialdehyde (MDA – impact of coenzyme Q10) correlated (with MPO-myeloperoxidase activity -generating ROS) as co-variable, by which mulberry leaf polysaccharide (MLPII) via the decomposition of (certain) MDA, products of lipid peroxidation (LPO) were reduced. Comparisons were to specific activities of catalase (SNP) single nucleotide polymorphisms (CAT-C-262 (rs1001179) the low-risk allele) of genetic variants in both, promoter a common C/T polymorphism (262-C/T), and in nineexonic – regions and its boundaries, occur frequently associated distally in genomic mutations, similar to those of normal catalase demonstrating changes in catalase protein level targeted to the peroxisomal matrix. The 262-C/T CAT low-risk allele is hypothetically related to the lower risk variant allele CAT Tyr308 G to A point mutation ineducable in the Japanese acatalasemia allele. The common C/T polymorphism can be targeted by dietary and/or pharmacological antioxidants, and the endogenous antioxidant defense enzymes concentration can prevent cellular lipid (LPO) peroxidative reactions occurring. Catalase is a homotetramer complex of 4 identical monofunctional subunits. Catalase is located at the peroxisome of human cells associated with several (PBDs)-peroxisomal biogenesis disorders commonly caused by mutations in the PEX genes, peroxisomal targeting signal 1 (PTS1) protein affecting in peroxisomal biogenesis, the monomeric to homotetrameric transition in the forms of peroxisome biogenesis disorder. PBDs also include Acatalasemia the only disease known to be caused by the (CAT) gene. In human catalase, the antioxidant heme enzyme, is localized in the cytoplasm to the peroxisome, nucleus, or linked with mitochondria which in most cells lack catalase (Peroxisomes do not contain DNA), its mitochondrial fraction (microperoxisome), a secondary phenomena shows physiological decline, aging and age-related reactions in mitochondrial function and disfunction. NADPH is required for the prevention of forming an inactive state of the enzyme. Antioxidative defence mechanisms, capacity and redox cycle enzyme activities increasing with Tc treatment Tinospora cordifolia (Tc), T and B cells and antibody. Both RBCs and plasma were measured on parameters of oxidative stress. Syzygium cumini aqueous leaves extract (ASc) was able to remove oxidant species in a hyperglycemic state generated in red blood cells RBC-CAT levels. Catalase alone is unable to prevent in a hyperglycemic state. Macrophages recruit other types of immune cells such as lymphocytes white blood cells (WBCs).  Catalase is dependent on the family of NADPH-binding catalases for function, the prevention and reversal of inactivation by its toxic substrate (H2O2) hydrogen peroxide. Amyloid-beta binds catalase and inhibits (H2O2) hydrogen peroxide, a reactive oxygen species, breakdown through efficient dismutation, and malonaldelhyde (MDA) determined in plasma, as well as another member of the oxidoreductase family, myeloperoxidase (MPO (EC converting H(2)O(2), the reducing equivalents produces (HOCl) hypochlorous acid a mechanism of cell-mediated antimicrobial immune defense for monofunctional catalases one of three subgroups related to catalase deficiency in humans, in micro-organisms manganese-containing catalases (‘large catalases’) determining in part the bifunctional activity of (KatG, PDB:1X7U) represented by bifunctional (heme) catalase-peroxidase based Bacterial-resistance mechanisms. Peroxiredoxins (Prxs, EC, bifunctional catalase-peroxidases (KatGs) two organelle systems are antioxidant enzymes of the peroxiredoxin family that oxidize and reduce H(2)O(2) hydrogen peroxide thereby modulating the catalase reaction, KatGs are not found in plants and animals. Trx (thioredoxin) a redox-regulating protein also controls the antioxidant enzyme activity of the main cellular antioxidant enzymes (AOE) superoxide dismutase (SOD) and catalase.
The function of NADPH bound to Catalase.
catalaseThe cytosine to thymidine transition of nucleotide-262 (-262C>T) Computer analysis indicated that the two variants bound promoter the Ile  (-262 C/T) and (B) Ile-262 in the 5′-flanking region carrying the T allele best captured and characterized the generation of the hydroxyl radical site in (PDB: 1DGB), (CAT) -[GLU] 330C>T transition, is known also as -262C>T. The ‘T allele in comparison to the C allele’ is a common C/T polymorphism frequency in the promoter region association was observed between genotypes for locus11p13 risk alleles acatalasemia mutation Asp (37C>T in exon 9) was hypothetically related to the lower risk Japanese acatalasemia allele Tyr308 a single G to A (see: rs7947841  to evaluate the link to rs769214) point mutation ineducable or near exon 9 (TC, CC, TT) of the CAT gene to which variant changes in the promoter region C/T-262 polymorphism are more closely related to CAT T/C at codon 389 in exon 9 (rs769217) polymorphism did not differ significantly from those of healthy controls in both promoter (-262 C/T) and in exonic (ASP389 C/T) regions of the catalase (CAT). catalase Tyr 370 resolves the 25 A-long (hydrogen peroxide) channel a constriction or narrowing of the channel leading to the heme cavity (‘Parameters) situated in the entrance channel to a heme protoporphyrin (ZnPPIX) (PDB: 1H6N) from a heme group, capable of heme biosynthesis‘ in a wide range of organisms convert it into into heme b, protoporphyrin IX-heme. Two channels lead close to the distal side.  A third channel reaching the heme proximal side Tyr 370, Ile-262 is proposed as a the ‘PDB: 1DGB – variant with a substituted residue in the ASP 178 to the (Met) D181E variant PDB 1p80‘.  These differences include the structure of the variant protein Val111Ala (Saccharomyces cerevisiae) related supports the existence of the ‘Heme and NADP(H) binding pockets’. The omission of a 20-residue  PDB: 1F4J, (1QQW) segment corresponds to the N-terminal (blue) of catalase from human erythrocytes (HEC), or in a C-terminal (red) domain organized with an extra flavodoxin-like fold topology may provide with weak coordination the N- or C-terminal, that allows scrutiny of the origins (topology) in this report of what would otherwise remain speculative or determined with further verification.
 Biological Xenobiotic Extracts Applications of note In the presence of Catalase:
green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG)
Yamamoto T, Lewis J, Wataha J, Dickinson D, Singh B, Bollag WB, Ueta E, OsakiT, Athar M, Schuster G, Hsu S. Roles of catalase and hydrogen peroxide in greentea polyphenol-induced chemopreventive effects. J Pharmacol Exp Ther. 2004Jan;308(1):317-23. Epub 2003 Oct 20. PubMed PMID: 14569057.Furukawa A, Oikawa S, Murata M, Hiraku Y, Kawanishi S. (-)-Epigallocatechingallate causes oxidative damage to isolated and cellular DNA. Biochem Pharmacol.2003 Nov 1;66(9):1769-78. PubMed PMID: 14563487.*
Trigonella (Fenugreek)
Mohammad S, Taha A, Bamezai RN, Basir SF, Baquer NZ. Lower doses of vanadatein combination with trigonella restore altered carbohydrate metabolism andantioxidant status in alloxan-diabetic rats. Clin Chim Acta. 2004Apr;342(1-2):105-14. Erratum in: Clin Chim Acta. 2010 Aug 5;411(15-16):1158.Mohamad, Sameer [corrected to Mohammad, Sameer]. PubMed PMID: 15026271.
Aegle marmelos
Khan TH, Sultana S. Antioxidant and hepatoprotective potential of Aeglemarmelos Correa. against CCl4-induced oxidative stress and early tumor events. JEnzyme Inhib Med Chem. 2009 Apr;24(2):320-7. doi: 10.1080/14756360802167754 .PubMed PMID: 18830880.
Centella asiatica
Flora SJ, Gupta R. Beneficial effects of Centella asiatica aqueous extractagainst arsenic-induced oxidative stress and essential metal status in rats.Phytother Res. 2007 Oct;21(10):980-8. PubMed PMID: 17600859.
Mishra P, Kar A, Kale RK. Prevention of chemically induced mammarytumorigenesis by daidzein in pre-pubertal rats: the role of peroxidative damageand antioxidative enzymes. Mol Cell Biochem. 2009 May;325(1-2):149-57. doi:10.1007/s11010-009-0029-1. Epub 2009 Feb 13. PubMed PMID: 19214712.
Yadav P, Sarkar S, Bhatnagar D. Action of capparis decidua againstalloxan-induced oxidative stress and diabetes in rat tissues. Pharmacol Res. 1997Sep;36(3):221-8. PubMed PMID: 9367667.
Kannan R, Jin M, Gamulescu MA, Hinton DR. Ceramide-induced apoptosis: role ofcatalase and hepatocyte growth factor. Free Radic Biol Med. 2004 Jul15;37(2):166-75. PubMed PMID: 15203188.
Cemek M, Caksen H, Bayiroğlu F, Cemek F, Dede S. Oxidative stress andenzymic-non-enzymic antioxidant responses in children with acute pneumonia. CellBiochem Funct. 2006 May-Jun;24(3):269-73. PubMed PMID: 16634091.
Diallyl disulfide (Allicin)
Kalayarasan S, Prabhu PN, Sriram N, Manikandan R, Arumugam M, Sudhandiran G.Diallyl sulfide enhances antioxidants and inhibits inflammation through theactivation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats. EurJ Pharmacol. 2009 Mar 15;606(1-3):162-71. doi: 10.1016/j.ejphar.2008.12.055. Epub2009 Jan 19. PubMed PMID: 19374873.
Leucas aspera (Catechin, EGCG)
Kripa KG, Chamundeeswari D, Thanka J, Uma Maheswara Reddy C. Modulation ofinflammatory markers by the ethanolic extract of Leucas aspera in adjuvantarthritis. J Ethnopharmacol. 2011 Apr 12;134(3):1024-7. doi:10.1016/j.jep.2011.01.010. Epub 2011 Jan 18. PubMed PMID: 21251972.
Urtica dioica (nettle suppliment)Ozen T, Korkmaz H. Modulatory effect of Urtica dioica L. (Urticaceae) leaf
extract on biotransformation enzyme systems, antioxidant enzymes, lactatedehydrogenase and lipid peroxidation in mice. Phytomedicine. 2003;10(5):405-15.PubMed PMID: 12834006.
Justicia adhatoda
Singh RP, Padmavathi B, Rao AR. Modulatory influence of Adhatoda vesica(Justicia adhatoda) leaf extract on the enzymes of xenobiotic metabolism,antioxidant status and lipid peroxidation in mice. Mol Cell Biochem. 2000Oct;213(1-2):99-109. PubMed PMID: 11129964.
Phyllanthus niruri L. (Euphorbiaceae) (P. niruri)
Bhattacharjee R, Sil PC. Protein isolate from the herb, Phyllanthus niruri L.(Euphorbiaceae), plays hepatoprotective role against carbon tetrachloride inducedliver damage via its antioxidant properties. Food Chem Toxicol. 2007May;45(5):817-26. Epub 2006 Nov 11. PubMed PMID: 17175085.
Tinospora cordifolia
Sharma V, Pandey D. Protective Role of Tinospora cordifolia againstLead-induced Hepatotoxicity. Toxicol Int. 2010 Jan;17(1):12-7. doi:10.4103/0971-6580.68343. PubMed PMID: 21042467; PubMed Central PMCID: PMC2964743.
Aher V, Kumar Wahi A. Biotechnological Approach to Evaluate theImmunomodulatory Activity of Ethanolic Extract of Tinospora cordifolia Stem(Mango Plant Climber). Iran J Pharm Res. 2012 Summer;11(3):863-72. PubMed PMID:24250513; PubMed Central PMCID: PMC3813135.
coenzyme Q10
Lee BJ, Lin YC, Huang YC, Ko YW, Hsia S, Lin PT. The relationship betweencoenzyme Q10, oxidative stress, and antioxidant enzymes activities and coronaryartery disease. ScientificWorldJournal. 2012;2012:792756. doi:10.1100/2012/792756. Epub 2012 May 3. PubMed PMID: 22645453; PubMed CentralPMCID: PMC3356738.
Dietary carotenoid-rich pequi oil
Miranda-Vilela AL, Akimoto AK, Alves PC, Pereira LC, Gonçalves CA,Klautau-Guimarães MN, Grisolia CK. Dietary carotenoid-rich pequi oil reducesplasma lipid peroxidation and DNA damage in runners and evidence for anassociation with MnSOD genetic variant -Val9Ala. Genet Mol Res. 2009 Dec15;8(4):1481-95. doi: 10.4238/vol8-4gmr684. PubMed PMID: 20082261.
Tinospora cordifolia  (Mango Plant Climber) extract from Tinospora known as Tinofend Aher V, Kumar Wahi A. Biotechnological Approach to Evaluate theImmunomodulatory Activity of Ethanolic Extract of Tinospora cordifolia Stem(Mango Plant Climber). Iran J Pharm Res. 2012 Summer;11(3):863-72. PubMed PMID:24250513; PubMed Central PMCID: PMC3813135.
 mulberry leaf polysaccharide (MLPII)
Ren C, Zhang Y, Cui W, Lu G, Wang Y, Gao H, Huang L, Mu Z. A polysaccharideextract of mulberry leaf ameliorates hepatic glucose metabolism and insulinsignaling in rats with type 2 diabetes induced by high fat-diet andstreptozotocin. Int J Biol Macromol. 2014 Oct 11. pii: S0141-8130(14)00674-6.doi: 10.1016/j.ijbiomac.2014.09.060. [Epub ahead of print] PubMed PMID: 25316427.
five widely studied medicinal plants (Protandim)
Nelson SK, Bose SK, Grunwald GK, Myhill P, McCord JM. The induction of humansuperoxide dismutase and catalase in vivo: a fundamentally new approach toantioxidant therapy. Free Radic Biol Med. 2006 Jan 15;40(2):341-7. PubMed PMID:16413416.
Mayo JC, Tan DX, Sainz RM, Lopez-Burillo S, Reiter RJ. Oxidative damage tocatalase induced by peroxyl radicals: functional protection by melatonin andother antioxidants. Free Radic Res. 2003 May;37(5):543-53. PubMed PMID: 12797476.
Protective effect of harmaline
Kim DH, Jang YY, Han ES, Lee CS. Protective effect of harmaline and harmalolagainst dopamine- and 6-hydroxydopamine-induced oxidative damage of brainmitochondria and synaptosomes, and viability loss of PC12 cells. Eur J Neurosci.2001 May;13(10):1861-72. PubMed PMID: 11403679.
horseradish peroxidase (HRP)
Shen L, Hu N. Heme protein films with polyamidoamine dendrimer: directelectrochemistry and electrocatalysis. Biochim Biophys Acta. 2004 Jan30;1608(1):23-33. PubMed PMID: 14741582.
Selegiline (–)Deprenyl
Kitani K, Minami C, Isobe K, Maehara K, Kanai S, Ivy GO, Carrillo MC. Why(–)deprenyl prolongs survivals of experimental animals: increase of anti-oxidantenzymes in brain and other body tissues as well as mobilization of varioushumoral factors may lead to systemic anti-aging effects. Mech Ageing Dev. 2002Apr 30;123(8):1087-100. Review. PubMed PMID: 12044958.
Rhodiola rosea
Bayliak MM, Lushchak VI. The golden root, Rhodiola rosea, prolongs lifespanbut decreases oxidative stress resistance in yeast Saccharomyces cerevisiae.Phytomedicine. 2011 Nov 15;18(14):1262-8. doi: 10.1016/j.phymed.2011.06.010. Epub2011 Jul 30. PubMed PMID: 21802922.
Kiziltunc A, Coğalgil S, Cerrahoğlu L. Carnitine and antioxidants levels inpatients with rheumatoid arthritis. Scand J Rheumatol. 1998;27(6):441-5. PubMedPMID: 9855215.
 Syzygium cumini
 De Bona KS, Bellé LP, Sari MH, Thomé G, Schetinger MR, Morsch VM, Boligon A,
Athayde ML, Pigatto AS, Moretto MB. Syzygium cumini extract decrease adenosine
deaminase, 5’nucleotidase activities and oxidative damage in platelets of
diabetic patients. Cell Physiol Biochem. 2010;26(4-5):729-38. doi:
10.1159/000322340. Epub 2010 Oct 29. PubMed PMID: 21063110.

Characterization of human thioredoxin system and the potential cellular responses encoded to observe the Thioredoxin-Trx1 reversibly regulated redox sites.

Thioredoxin: human TXN, is a oxidoreductase enzyme in the status of a 12 kDa cellular redox-reductase reaction (70-kDa in bacteria, fungi and plants), a cellular defense mechanisms against oxidative stress of the cell, and numerous cytosolic processes in all cells. Txn1 is a pleiotropic cellular causative gene factor which has numerous functions. Chromosome 3p12-p11 shares homology with human thioredoxin gene Trx1, Trx80: 9q31.3; (§, ). Here the following reaction is the possible mechanisms of the thioredoxin-catalyzed reduction and re-oxidation of its characteristic cystine residues.

 The TXN gene, consists of the first of 5 exons  separated by 4 introns and is located 22 bp downstream from the only known basal TATA box factor TBP-2/TXNIP vitamin D(3) up-regulated protein 1-VDUP1, negatively regulating TRX function, and exhibiting cellular growth and suppressive (cancer) activity.

 TRX inhibited Apoptosis signal-regulating kinase-ASK1 kinase (MAP3K5), activity, dependent on two cysteine residues in the N-terminal domain of ASK1 on the redox (regulation) forming intramolecular disulfide between the status of TXN. Two cysteine residues (N-terminal C32S or Trx C-terminal C35S and/or a Trx-CS double mutation) remaining trapped with the Ask1 as a inactive high-molecular-mass complex, blocking its reduction to release Trx from ASK1 depends on intramolecular disulfide to catalyze the reduction of the redox regulation of TRX. Trx and a thiol-specific antioxidant thioredoxin peroxidase-2 orthologue (Tpx) in various* biological phenomena is involved in redox regulation (NADPH-the thioredoxin system) of the dithioldisulfide active site.

 An apoptosis signal transduction pathway through stimulus-coupled S-nitrosation of cysteine, has two critical (almost identical) cysteine residues in the Trx redox-active center. Where a disulfide exchange reaction between oxidized Txnip [thioredoxin-interacting protein; mouse Vdup1] and reduced TXN occurs. Txnip (-when used to investigate cardiac hypertrophy) is a regulator of biomechanical signaling. Hydrogen peroxide downregulated expression is the only known function associated with an incomplete TRX response through stimulus-coupled S-nitrosation of cysteine residues. Peroxiredoxin PrxIII-‘Tpx1 serves as’ a tandem (dimer) thioredoxin (Trx2) and NADP-linked thioredoxin reductase (TRR2-TxnR1), are Trx mechanisms of the two electron donor system.

 Cytosolic caspase-3 was maintained by S-nitrosation, consistent with cytosolic and mitochondria, Trx-1 contain equivalent Trx systems, which enabled identification of caspase-3 substrates where TXN may regulate S-nitrosation with the redox center of TXN specific (C73S) to Nitric oxide-NO cellular signal transduction associated with  inhibition of apoptosis or mutant Trx neurotoxicity. EGCG° (epigallocatechin-3-gallate) may be useful in cell survival on caspase-(3_dependent)-neuronal apoptosis where a membrane reaction, a reduced hormesis consequently triggers the apoptosis effect and direct or indirectly numerous protein-protein interactions and basal cofactor substrates which occur between caspase-3 and Trx. The effect of  exercise training via activation of caspase-3 has a decrease in superoxide, and increase of Trx-1 levels in brain. Protection from mechanical stress identified, NSF- N-ethylmaleimide transduced into a TRX peroxidase response via mechanical force of a typical transnitrosylated  Casp3, attenuated  Trx1 2-cysteines which directly transnitrosylates Peroxiredoxins. C32S ( redox potential) was identified as thiol-reducing system, which lacks reducing activitiy (nonactive C69S and Cys(73) both monomeric) or a reversible regulating function in the presence of caspase 3 activity is a process found in the presence of NADP and TrxR.

 There are at least two thioredoxin reductive or oxidative** (reductases / peroxiredoxin) regulated systems. The mutant 32CXXC35′ motif of thioredoxin nitrosation sites, where two cysteines are separated by two other amino acids, and codes for an additional three cysteines where the Cys 62/C73S (not monomers) sidechain the active site of Cys 62 also can form several disulphides and be modified by the carbon-bonded sulfhydryl, where the  thiol reducing system, was evident.

 Intracellular TRX/ADF (Adult T cell leukemia-derived factor HTLV-I) can regulate cell nuclei, protein-nucleic acid interactions. Transnitrosylation and denitrosylation is a reversible Post-translational (PTM) altered by redox modification of different cysteine residues (C3273S) in Trx1, S-nitrosation or its interactions with other proteins and DNA-dependent nuclear processes. NFKappaB REF-1 redox factor 1  involving Cys62, in the two complexes, are correlated as N ⇔ C-terminal responses with  TRX-1 nuclear migration through the reduction of a pleiotropic cellular factor. TRX redox activities of protein-protein cysteine residues is identical to a DNA repair enzyme through various cytoplasmic aspects mediating cellular responses in the ‘nucleus‘. The DNA binding activity and transactivation of ‘AP-1‘ activator proteins (JUNproto* oncogen) depends on the reduction between the sulfhydryl of cysteines to keep Trx1 reduced, is demonstrated in cells. Selenium-dependent seleneocysteine based peroxidase reductants, reduce Lipoic acid stereoselectively under the same TRX rather than GSH-PX1-glutathione peroxidase oxidative stress conditions. Senseantisense (TRX) antiapoptoitic interactions nitrosylated at Cys73 are attenuated and integrated into the host cell under oxidative conditions, in which thioredoxin (TRX), and a cellular TRX reducing catalyst agent (DTT-redox reagent) to S-nitrosoglutathione (GSNO) intermediate via cysteine residues ‘influences’-catalyst mediated (post-translational modifications) PTMs; and possibly 1,25D(3)-Calcitriol; NADPH:oxygen oxidoreductases correlated with  (Trx-1) a protein disulfide oxidoreductase.

 Peroxynitrite** converts superoxide to hydrogen peroxide (H2O2)-induced Trx degradation, in concentrations that detoxify reactive oxygen species (ROS), demonstrated by superoxide dismutases (SOD)-catalyse and peroxidases, converting superoxide to hydrogen peroxide which is decomposed to water plus oxidized thioredoxin to maintain the anti-apoptotic (C62) function of thioredoxins additional five sulfhydryl group thiols in the fully reduced state, in a Trx-dependent manner. Reactive oxygen species (ROS) can cause DNA damage, and uncontrolled cellular proliferation or apoptotic death of cancer cells.The NADPH (Trx system) oxidizing substrate-dependent reduction of Thioredoxin reductase-TrxR has a reversibly modulated role in restoration of GR (glucocorticoid receptor) function, and DNA binding domain.

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NADP  1XOB Secreted Trx may participate in removing inhibitors of collagen-degrading metalloproteinases. PMID: 14503974 the molecular mechanisms underlying functional the TR1-Trx1 redox pair and structure determination of an active site of the ligand mini-stromelysin-1 TR-1 augmentation composed of TR (Trx reductase activities) the main function of TR1 here is to reduce Trx1 also validated as a ligand PMID; 23105116, have been characterized between ligand bound and free structures PMID; 20661909, for specific isolation of  C35S selenocysteine (SeCys)-containing protein shows the best docking position found, consists of one strand at position [PROline]76:A.side chain: from the four-stranded antiparallel beta sheet was with wild-type TrxA C32-35S located in the Thioredoxin_fold (PDB accession code 1XOB: PMID: 15987909) , TR1 as a single hybrid PDB (Cys32 and Cys35 for Trx1, and for TR1) pubmed/20536427 investigate the possible mechanism. {{{During this reduction, the thiol-disulfide oxidoreductase thioredoxin-1 (Trx1) linked thioredoxin reductase (TRR2) a working model suggesting that deregulation of the thioredoxin reductase TXNRD1 and|}}} its characteristic substrate thioredoxin (TR [1]), concomitant with diminution of their Trx reductase cellular contents is highly related to glutamate excitotoxicity PMID: 20620191; TR1: hStromelysin-1

enlargeNADPAn ET (electron transfer) mechanism from NADPH and another  enzyme thioredoxin reductase pubmed/17369362 the charged residue aspartate D60 (Fig.2) pubmed/9369469/ plays a role in the degradation of proteins and in apoptotic processes induced by oxidative stress  PMID: 16263712  to determine the effect of  zerumbone ZSD1 Zerumbone-loaded nanostructured lipid carriers Int J        Nanomedicine. 2013;8:2769-81. doi: 10.2147/IJN.S45313. Epub 2013        Aug 2 PMID:23946649 [PubMed - indexed for MEDLINE]        PMCID:PMC3739459 (from shampoo ginger; Name: Alpha-humulene) on NADP-malate dehydrogenase, TRX dependent oxidoreductase, that NADPH does not contain. Monomeric Thioredoxin is present across phyla from humans to plants PMID: 20661909, 11012661 mediated in vivo by thioredoxin-catalyzed reduction and re-oxidation of cystine residues PubMed id: 10196131 (Fig.3-PDB: 1CIV, NADP). Trx is able to activate vegetal NADP-malate dehydrogenase PMID: 3170595 (excluding the initial methionine) Met is located at the N-terminal – PMID: 11807942, 2684271. A relatively rigid local configuration for the aspartate residue D60 is found but which implies that the (NADP-TrxR) protein fluctuates among the numerous protein models and mutations over the time scales fluctuations.

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Gluathione peroxidase (GSH-Px1-GPX1) a extracellular selenoenzyme expression modulates xenobiotic metabolising enzymes.

     Glutathione peroxidase (EC protects against oxidative damage via the chemoprotective action of nitric-oxide mediated lipid peroxidation and anti oxidative defense by gluathione (GSH-Px1-GPX1) a extracellular selenoenzyme, extracellular glutathione peroxidase (E-GPx) and cellular (C-GPx) detoxifies hydroperoxides. Other antioxidant genes (AOX) as Gpx1, is located in the cytosol and in (mt) mitochondria. Epithelial antioxidative enzymes (AOEs) are activities of GSH-Px1 (gluathione peroxidase), (SOD) superoxide dismutase, and thioredoxine reductase (TXNRD1) by itself or with thioredoxin (Trx) are antioxidant enzymes. Glutaredoxin (Grx) are reduced by the oxidation of glutathione an antioxidant, (The effect of iridoid  glucosides such as oleuropein an antioxidant, can often be bound to glucose.) phenolic compound isothiocyanate sulforaphane found in olive leaf, increased cell-lysate NAD(P)H:quinone oxidoreductase (NQO1) phase II activities reduction reactions, catalyzed such as by glutathione-S-transferase (GST) can catalyze the conjugation back to the the thiol group and other GPx mimics (converted into selenocysteine), to the reaction site of glutathione (GSH) and antioxidants, implying (GR) reduction reactions back to glutathione, are an evolutionary relationship between GST and GPx/glutathione system defense in oxidative stress. “Glutathione” peroxidase (Gpx) content, and glutathione reductase (GR) components compose the glutathione (GSH) system, this contains Selenocysteine (Sec), the 21st amino acid at the active GPX site (Homo sapiens chromosome 3, GRCh37 primary reference: rs644261)- TGA  => UGA (selenocysteine, which occurs at the active site of  glutathione peroxidase GPX1 is coded by UGA, isoform 1 NM_201397.1-variant 1 represents the shorter transcript that  encodes the longer isoform 1, as compared to isoform 2– NM_000581.2 variant 2); (rs1050450) is intronless and has a shorter C-terminus. They represent the cDNA as a molecular mechanism (TGA) for down-regulation of mRNA expression and transcriptional code is a regulatory switch at the translationalstep delivered to the ribosome in genes similar to Glutathione peroxidase 1 (GP, Gpx1, GSHPX1): locus 3p13-q12 (§, ,). GSH-Px is an essential nutrient selenium dependent GPX, by which mRNA translational repression of selenium-binding protein (SBP1) is accomplished when GPX1 increased in human plasma, if selenium-deficient, while independent of Se values in leukocyte (White blood cells) from correspondingly damaged DNA. In fibroblast activity, GPx1 was effective through the prevention or repair of DNA damage. The reductive detoxification of peroxides in cells modulates xenobiotic metabolising enzymes via anticarcinogen supplementation, e.g. selenium-yeast  in human plasma. GPX in turn, can lead to carcinogenesis. The heterozygote has an intraerythrocytic environment (red blood cell) with the favorable higher peroxidase activities role in malarial resistance. An in-frame GCG trinucleotide repeat was homozygous for the pseudogene GPX1 Pro197Leu-like two alleles associated with 6 GCG repeats coding for a polyalanine tract. CuZn-SOD (copper/zinc-superoxide dismutase) and other oxidoreductases contribute to the cellular defenses, repair of oxidative damage to DNA. Chronic hyperglycemia (excessive blood sugar) causes oxidative stress, ‘Extract silymarin and Berberine-‘may‘ overcome insulin resistance. And for diabetes Astragalus membranaceus  can improve the protective effect, an extract from Shidagonglao roots (Mahonia fortunei)  or the effects of Berberine from the main alkaloid of Coptis chinensis  are agents for preventing sepsis and its lipopolysaccharide (LPS) complications in human microvascular endothelial cells. GPX is down-regulated and peroxiredoxin (PRX) is up-regulated. Both use thioredoxin (Gpx and Prx, suppress Trx, a cysteine-based thioredoxin-specific GPx-Txn expression.) to recharge after reducing hydrogen peroxide (H2O2) along with other cellular molecules. Also found in transcripts in ocular tissues from oxidative anterior damaged cells,  GSH-dependent recombinant human lens thioltransferase (RHLT)* being  its repair systems. GPX1 could supress staurosporine-induced late generation of ROS, corresponding to reduction in visual loss.  Its role in pathogenesis of  (inflammatory disorders of blood antioxidant enzyme system) as an autoimmune disease background, appears to be the hydroperoxide metabolism in diverse pathogens*, an enzyme by single administration streptozotocin  (60 mg/kg) of negative implication, oxidative damage or antioxidant status when examined in contrast as metabolic syndrome through the GPX downregulation are comparable, with reduced-enzyme-activity to the T allele of the GPx-1 genetic leucine/proline polymorphism at codon 198  approximately 70% for pro197 and 30% for leu197 named Pro198Leu (rs1050450). The leucine-containing allele was less responsive to GPx-1 enzyme activity. Thioltransferase (TTase) with GPx the dethiolating enzyme, thiol* catalysis glutaredoxin thioltransferase (Grx) content and activity to the thiol status produced by the oxidation of glutathione: a seleno-organic compound ebselen  (2-phenyl-1,2-benzisoselenazol-3(2H)-one) catalyzed in vitro, has been reported to ‘« mimic » development of small-molecule selenium compounds’ (‘synthetic antioxidant’ GPX)  required for, a diphenyl diselenide PhSe group ‘in the catalytic activities’ is introduced by reaction (a monocyte-derived soluble protein (M-DSP/Gpx1) with 5-LO, (5-lipoxygenase ) activity this ‘recovered (M-DSP)-GPx inactivation’. In which Serum Malondialdehyde (MDA) a marker (oxidative activity) generated from, reactive oxygen species (ROS) is thought to cause DNA damage with various antioxidants usually homeostatically controlled by endogenous superoxide dismutase (SOD), as a by-product and the oxygen-sensor neuroglobin (Nb), GSHPx reactive neurons or in brief neuronal damage (apoptosis) after ischemia. Antioxidant enzymes such as Cu/Zn-superoxide dismutase (SOD) and a 21-kD protein (involved in neuroprotection) GPx1 both in the free radical chain, protects neurons and Microglial cells. Microglial cells are, sensitive to small changes from Reactive oxygen species (ROS), free radical scavenging enzymes-mediated apoptosis. Neuronal loss and deteriorating CNS function: is linked to the pentose phosphate shunt, the (PPP) pentose phosphate pathway, has a relatively low content of enzymatic antioxidants, in a higher cellular ROS level to oxidative stress. A candidate (SePP1) selenoprotein (P-plasma) or  genetic variations homologous to GPX1 are rapidly degraded at relative low selenium concentrations. Microsomal (reconstituted fraction) glutathione transferase-1 (hGSTP1) decreased cytotoxicity ( cartilage degradation and regeneration [Leucas aspera] to mitochondria damage, directed to citrulline- containing proteins) by effects of hydrogen peroxide ‘H(2)O(2), which causes lipid peroxidation (LPO) in the (ER) endoplasmic reticulum. In which LPO product Malondialdehyde and other Thiobarbituric acid reactive substances – TBARS – are formed as a byproduct, when the effects of GPX1 ( glutathione peroxidase 1)’ is measured, the effects of Centella asiatica  extract detoxifies. Antioxidants and detoxication agents as antigenotoxic* agents (isoflavones via dietary intake) were also observed as cytogenetic end-points* of carcinogenesis. Over-expression could drain the  reduced glutathione ( hepatic and GSH dependent enzymes), cellular glutathione (GSH) levels, GSH acts as a feedback rate-limiting inhibitor of its synthesizing enzyme GCL (gamma-glutamyl-cysteine synthetase) activity,  Diosgenin  is a useful Marker degradation-compound of Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) against oxidation. The compound buthionine sulfoximine (BSO) inhibits the first step of glutathione synthesis, concerning the mechanism of GSH depletion. Gpx suppresses (thioredoxin) Trxexpression, which augments Anti-clastogenic (mutagenic agents), potential DNA-binding (heritable multigenerational/evolutionary tolerance), in a cDNA open reading frame (ORF) GPx1 is a small inversion (~pericentric), incorporating the co-translational selenocysteine which may be unique to the insertion sequence elements.
      gpx1Biological Assembly GPx-1 tetrameric structure with an altered carcinogen metabolism and reduce oxygen tension to explain the anti-carcinogenic effects, the redox donor (hTXN-oxidoreductase) status  (Figure 2) of one oxygen atom limited to only two regions may carry missense variant (rasmol_php_C and _D) a reaction incorporated into the overall tetrameric structures instability potentially in humans through modulation of biosynthetic and genetically modified GSH enzymes binding the selenocysteine insertion sequence elements. The specific activity of the enzyme Sec suggest how the molecular pathway might work, as the glutathione pathway may influence the enzyme Sec reaction site incorporation sequence in the 3′-untranslated region UTR of glutathione (GSH) may further reveal a signaling pathway that is activated. The differing and interacting roles of GPX1 and (Sec.) Selenocysteine Synthase [doi: 10.2210/rcsb_pdb/mom_2008_8] both vectorsgpx1together with glutathione (HUMAN GLUTATHIONE TRANSFERASE (HGST) PDB ID: 1LJR ligand component GSH: C10 H17 N3 O6 S, molecules colored: aquamarine) did; activates two multiple signaling pathways in one of the Gpx1 variants 1 or 2 nucleotide, the nonsense codon, UGA has both, related to the antioxidative pathway vectors together PDB ID: 1gp1 (2-AMINO-3-SELENINO-PROPIONIC ACID: ALANINE  molecule colored: purple), is located near the selenocysteine insertion sequence element PDB ID: 2F8A (rainbow colored: ribbons) mutant of  GPX1. Interrogation of data based on experimentally determined models are limited but revealed network structures that dynamically conveyed information from the antioxidant enzymes that share a common pathway considered most important in the selenocysteine synthesis pathway from the information suggested, and they implicate at least one selenoprotein (GPx-1) in the process.

G6PD, Exon 12 is an exonic splicing silencer containing/substituted define codon regions involved in the G6PD mRNA¹

G6PD (EC glucose-6-phosphate dehydrogenase [§§; , ], situated at Xq28 locus-coding region is the ratelimiting enzyme, of the (PPP) pentose phosphate pathway. G6PD deficiency  and its  X-linked gene mutations exons 2-13 (160 different mutations) are the most common inborn error of metabolism, in human red blood cell (RBC) enzymopathy, among humans. G6PD is divided into 12 segments and involves an exonic splicing enhancer (ESE) in exon 12 with 13exons and an intron present 5′ UTR, proximal to the 5′ bkp-breakpoint region. Intron comparisons from the second to the thirteenth exons of G6PD gene, 3′ UTR towards the 3′ end of the gene to exon 1 located in 5′ UTR G6PD is a region of deleted alleles (ASO-PCR) or G-6-PD the many population genetics variants/wild-type (160 different mutations and  300 G6PD variants) assuming that, at exon2 (2,3-BPG* levels) are hypothesized that G6PD partly ‘overlaps’ the IKBKG gene confined to the blood. The subunit (G6PD), consists of the biochemicalcharacteristics of 531 amino acids. This enzyme is the only process in mature red cells for NADPHgeneration it involves oxidation of glucose as a » hexose « ( xenobiotic compounds) pathway (‘naturally found in D-* and the unusual L- Monosaccharide forms or between 2,3-BPG*) pentose and hexose phosphates, an alternative to glycolysis, converts glucose in which ATP is produced’ from the conversion of glucose-6-phosphate into ribulose 5-phosphate in liver cytosol in which a residue in the dimer interface (@ 37° C) structural G6PD is a NADP+ dependent. At the tetramer interface an Apoenzyme (PDB:2BH9), that stimulates G6PD to produce (reversible enzyme transketolase (TK) presence is necessary) more NADPH. Hemolytic crises or dysregulated NADPH oxidase located in the 3‘ dependent 5’ UTR G6PD in humans determines the response, in which G6PD deficiency is prevalent with development of  chronic hemolytic «« anemia (CNSHAHNSHA) associated with food-induced or a exogenousagent and druginduced ºª hemolytic crises which led to the discovery of G6PD deficiency. Sulfatase  (STS, EC catalyzes Phenyl-Piracetam  it also stacks well  and involves the phosphoinositide 3-kinase (PI 3-kinase) pathway in the employed doses in related induction of certain enzyme (Glucose 6PD) synthesizing activities (glycolysis) five metabolite levels of  insulin signal transduction. These include, Sulforaphane  or broccoli-sprout extracts increased cell-lysate NAD(P)H:quinone oxidoreductase (NQO1) phase II activities (Tanshinone IIA⊕), administered to cells and  in human supplementation studies, were found to be in balance with green tea extract (GTE), (EGCG) epigallocatechin-3-gallate   to generate detoxifying reactions to hepatotoxicity (can be prevented by amalika, Emblica officinalis   which supports the chemopreventive action of the silymarin extract Silibinin , of the milk thistle) preventing nitric oxide-mediated lipid peroxidation (LPO) and antioxidant defense system (GSH) glutathione ( GSH-Px and GR) depletion, via an antioxidant response element (ARE ⊕) mechanism-based inhibitor, element (NRF2) regulates (ARE)-regulated genes. A lack of NQO1 protein predisposes cells to benzene toxicity and to various forms of leukemias and toward therapeutic modulation (Acetylcysteine  and acetaminophen) of pulmonary oxygen toxicity. G6PD-deficient variants is the result of  various enzymopathies (but not GPI-chronic hemolysis), that glucuronidatedbilirubin values (UGT1A1 genotype) tended to parallel, (CNSHA) hyperbilirubinemia with hemolytic anemias, single amino acid substitutions resulting in ‘mutation of variants’. Or to inherited³ and acquired physiologic changes in red cell enzyme G6PD deficiency leading to favism ( an A- variant reaches the polymorphism level the commonest a Mediterranean form, other alleles A, A+, the primordial human type B cell and normal B+ and a rare B- phenotype are neutral. Malaria-infected human red cells possess at least two pathways (in a dimer — tetramer equilibrium) where carbonic anhydrase (CA) isoenzymes (allozymes are variants often neutral)  the native structure may serve different roles [malaria resistance] in the G6PD-deficient erythrocyte) and transmitted biochemical poly(A) characteristics (58 different -missense-mutations account for 97, poly(A) -substitutions-towards mutation of variants) divided into 5 classes of energy metabolism {chart} enzymes. Where GSH represents red cell enzymes involved in glycolysis, enolase (ENO), phosphoglycerate kinase (PGK), phosphofructokinase (PFK  that phosphorylates fructose 6-phosphate (PHI)),  hexokinase (HK), aldolase (ALD), and pyruvate kinase (PK)) activity. From class 1–chronic variants with administration of 8-azaguanine to class IV–increased enzyme activity. NADP-linked enzymes, malic enzyme (ME, EC malic dehydrogenase (MDH) that catalyzes  (NAD-ME) by the chemical reaction to NADP-ME and ATP:citrate lyase (ACL) and (IDH)-isocitrate dehydrogenase (NADP-ICD) channeled NADPH into the fatty acid biosynthesis influences carbohydrate metabolism and partly account for stimulated nucleotide synthesis. Poly(A) RNA  by carnitinepalmitoyl (CPT) and acyl (ACO) mRNA, or HMGCoA oxidase donating activities in inhibition of meiotic maturation, acetyl-CoA carboxylase (ACC) was also measured in the forming DNA adducts. The metabolism of xylitol remains intact to complete the NADPH cycle.  The G6PD gene is X-linked, G6PD synthesis leading to G6PD deficiencies which occurs in the oocyte where X-inactivation ( Xq13-XIST; 314670) large deletions or a loss-of-function mutation does not occur or might be lethal, had affected the red cell and white cell series differently, in the mouse presumably the polymorphisms of hemoglobin are on the X chromosome in man, according to hybrid cell studies of a number of domesticated species.

  Exon 12 is an exonic splicing silencer containing other-(exons II, III-IV, V, VI-VII, VIII, IX, X, and XI-XIII)-spliced exons regions and an exonic splicing enhancer (ESE) in exon 12. Using the G6PD model, Exon 12, may define 12 base pairs, or two DNA base substitutions in the deamano-NADP (EC utilization. g6pd

A regulatory element within exon 12 controls splicing efficiency and the rate of intron removal. The UGT1A1 gene and the exon 12 of G6PD gene and the polymorphisms of UGT1A1 two DNA base substitutions C1 and C2 for example Gly71Arg from Arg to His are the mutational activities (dimer pink PDB: rasmol_php SNP: L235F, Figs. 1-2 and 3) of serine-arginine-rich (SR), proteins located in exon 12 of the G6PD gene.

g6pd The most common mutations are: 1376 G–>T substitution abnormality (C1) and 1388 G–>A (G6PD Kaiping) abnormality (C2) is A–>G in exon2, both in exon 12 binding to the C-rich motifs (ESE) blocked binding of  the serine-arginine-rich splicing factor 3 (SRSF3) but not SRSF4, PDB-2I2Y.

g6pd Where G6PD partly ‘overlaps’ the IKBKG gene PDB: 2JVXblue-cartoon located in  the ribbon with the ESE-red-exon (XII) 12. The G6PD gene is 18 kb long divided into 12 segments ranging in size from 12 base pairs to 236 bp and interacts with elements in the beta-globin HBB common polymorphism site C1311T/IVS-II promoter are more common forms of the protein hemoglobin in the beta-globin HBB derived from the 3′-end of intron 7 is one of the 2 types of subunits in human red cell (RBC) G6PD. An ratio between heterozygote and hemizygote in males and between hetero and homozygote in females of cellular components evident from the state of G6PD activity modified by the rate of  (GdX PMID: 8786131, PDB:2BH9  a deletion variant of G6PD PMID-17637841) intron removal , shows that an intron present on the 5′ UTR (located on Fig. A, the end of blue cartoon situated near the broken blue strand) of G6PD the first intron of the G6PD genome isozymes can be observed, ‘GdA and GdB‘³ can be bound by NADP by a direct source of ROS effects of high glucose, inhibition of PKA decreased ROS can use a direct repeat-3 (DR3) vitamin D response element liganded vitamin D receptor.


Intra- and interchromosomal interactions of point mutations occurring in the vicinity of the normal 5-and 3 ends via low and high O(2)-affinities on the beta-globin complex.

Beta-globin (HBB) locus: 11p15.4  [§§; , -(HbS)] intra- and interchromosomal interactions with element in the beta-globin HBB is one of the 2 types of an asymmetric purine : pyrimidine sequences in beta-thalassemia patients (Hydroxyurea) and normal (nonthalassemic) individuals from the standard neutralmodel, to any one or more of 200 different mutations (unstable free globin chain subunits), a heterotetramer subunits assembly composed oftwo α-hemoglobin chains and two β-hemoglobin chains. In adult (Hb) hemoglobin, the IVS2intron“‘ promoter a coregulator of the GATA1 can serve a similar function as NF-E2 here; chromatinized minichromosome associations in erythroid cells. These data indicate (CTCF-CCCTC binding factor, interactions affects spatial distances) observations that favor EKLF’s red cell (RBC) activators erythroid specificity.  A self-organizing process, proposed role activates an adjacent promoter as both (human fetal (gamma)-to adult (beta)-globin) are important, however not sufficient (basal) stabilizing interactions,  -both were in cis and in trans distinct from alpha-globin mRNA, the 2 types of polypeptide chains interrupted by 2 intervening sequences the so-called** “switch“* region (that is, gamma—-beta -the average zeta potential, of externalized phosphatidylserine minimal for zeta-globin HBZ  dissociation constants (fast or slow* moving), to an embryonic alphalike hemoglobin),.  Gene-proximal acting cis-regulatory DNA elements (chromatin) are maintained that contain informative mutations ‘one’ on the 3-prime side of the beta-globin gene ‘and a leftward’ rate of neutral mutation (in the 5-prime direction) the centromere (beta-globin within the chromatin domain) which contains a ‘hotspot‘ (mutations causing diseases at HRAS1, D11S at one or more 11p15.5 loci in the HBB region from D11S and IGF2: INS are systems found to be dependent on EKLF ) for recombination in the HBB gene region 3-prime to the beta-globin gene (β-thal) mutations (led to DAPI lentiviral vectors (LVs) particles expressioncassette detection: genetic diagnosis (PGD) Preimplantation. And targeted integration of the adeno-associated virus (AAV).) at 5-prime splice sites (A gamma-) globin (HBG1) are held to be responsible for human genetic disease of fetal ‘Aγ and Gγ’ hemoglobin (HPFH/beta o-tha the BCL11A variant is associated with the same variable HbF) by (tagging with GFP) a single initial deletion followed by spread of the mutation, naturally occurring allele-(HardyWeinberg principle),  locus with two alleles denoted, and a second abnormal allele of an HBB mutation (e.g.,  the sicklecell haemoglobin gene Hb S, a naturally occurring mutant Hb C, β-thalassemia), with subsequent crossovers between the 5-and 3-prime and gene conversion and the creation of 2 others (e.g., Comparison‘s of the normal 5-and 3 ends, the processive region 3′ to the 3′ UTR messenger mRNP complexes ribonucleoprotein breakpoint via mutations or HS deletions (β-globin HS5 or 3′HS1) that contributes to the abnormal expression, or as RNA stability, maturation and transcriptional termination) for recombination (crossing-over or gene conversion) both in cis and in trans intra- and interchromosomal interactions of point mutations occurring in the vicinity of the beta-globin complex,  in cis to the gene mutations, were physically intact. SATB1 takes part in affecting the HBB higher order chromatin structure Matrix attachment regions (MARs) within the locus control region (LCR located at the 5′ end, flanked by AAV),  the HS2 and 3′HS1 active chromatin hub (ACH), remote 5-prime element genes (a member of the HMGB-2 high-mobility group protein 2 family) in cis to the deletion a single initial deletion is the beta zero type of  a coexisting thalassemia component and if so, if it is α-thalassemia or Beta (gamma-betaThalassaemia and (SCD-Hemoglobin) Hb SS anemia, sickle cell disease) and malaria  has some protective effect from increased risk of G6PD deficiency, with beta-globin co-inheritance a fetal adult gene as a cofactor involving the first non-coding near the 5-prime end of 3 exons  plus a single pseudogene termed psi beta 1 ( epsilon, beta and gamma are complementary to the structure of genes is coincidental of site mutants that are turned on and off ( H3 acetylation-(H4/R3* in the R state having T/R** low and high O(2)affinities)-K4 demethylation) the mechanism is more complex as development proceeds) the Dominant Control Region (DCR) and introns“‘ 1-5 both single nucleotide“‘ substitutions of the beta-globin gene to the deletion ‘in cis‘ a region designated LCRB, locus control region. (INS) the insulin gene was also mapped to this same region.


(1)  the “hinge region” of the alpha 1 beta 2 interface PMID: 1567857 were partitioned into components of ( PDB:1J7Y_colored in reds is Hb-alpha ) SNP PDB:1IRD HBA1 and 2 structure rearrangement,  the interface from the mutation site is site (B) about protein sequence 4L7Y-B alpha and D-beta: Resultsare for rs33930165 on Reference Sequence: NP_000509.1 [PMID: 22028795] attainment number P68871 verified by refinement of the a entire  molecule was confined to residues at the central cavity close to the 2,3-DPG found in the NP_000509.1 hemoglobin (PDB: 4L7Y) subunit beta. 1J7Y_Reds Hb-alpha,_Blues Hb-beta. With The effect of mutagenesis on O(2), CO,                   and NO binding to mutants 1J7Y HBB.H116R_D test Disease GeneHBB  protein/NP_000509.1structure arrangement. The alpha (HBA) and beta (HBB) loci determine the structure resolution analysis reported here implies…  the structure of genes is

coincidental of site mutants that are turned on and off ( H3 acetylation-(H4/R3* in the R state having T/R** low and high O(2)affinities)-K4demethylation) the mechanism is  more complex as development proceeds) e.g.  not present in the final mature HBB gene product.





(2)  Behaviour of a natural haemoglobin and a mutant variant in the central cavity close to the 2,3-diphosphoglycerate pocket  4L7Y-D a band migrating in the Hb F_ a solvation band-position-PDB: rasmol_php (DiseaseE6K_33930165_F_[solvent- is nonbonded spheres on 4L7Y-D Hb-beta Red fig. (1)) and its reactions with 2,3-DPG and inositol hexaphosphate-PMID: 6526653: accounts for the reduced oxygen affinity of haemoglobin;  by the oppositely charged side-chains residue that project into or are missing in the heme pocket, and result in a thalassemic and/or hemolytic -like phenotype the result of decreased alpha 1 beta 1 interactions.


HBB Network visualized with Cytoscape. The inverse of the inverse not inferable from Figure (4) overlaps the hinge region for exon selection 3’5’duplications. pubmed/21269460 [#35]




 (3) 4L7Y-B inhibits the rate of ligand binding HIS’147 the native imidazole side chain is 4L7Y-D modification at each site is a function of the position of these 2 hemoglobin alpha and beta introns the electrostatic attraction or repulsion by the oppositely charged side-chains therefore the efficiencies of intron 1, PMID: 6599969 and intron 2, PMID: 16184579 are unaffected residue near the 3′ end (Blue color) (4L7Y_B/B/LEU’3/CA) of the intron on a mechanism that measures the distance, the first intron might facilitate splicing (aligned as B-D, B-D) of the second intron (Orange) 4L7Y and desease HBB locus gene in which intron 1 PMID: 18266765 accommodates the 5′ end (Orange). Introns are not present in the final HBB gene product mature RNA with SNP: rs33949930,                   amplified from exon (Blue) 1 + 2 (PMID: 8226093) of the beta-globin gene: NG_000007.3(a neutral mutation [ SNP: rs33949930                   Position 70599]). Present in SNP to nucleotide allele T.


(4)  Correlated inversely. The intron is linked both in the intron-exon sequence and nearer the (Blue) 3′ end (an adaptation to endurance PMID: 16990440 ) of the intron upstream from the 3′ terminus to the 3′-side of the beta-globin gene PMID: 478302 of the intron (Orange) on 4L7Y-B beta-globin gene should remain active together with all other (PMID: 11559912 alleles) forms of the same HBB gene multiallelic loci  PMID: 15315794 involved in beta-thalassemia along with the unrecognized allelism found in  PDB:1IRD among a new neutral mutation. V2E, A, G, L, SNP 33949930 (hydrophobic interaction decreased; hbb hbb )  the single nucleotide polymorphisms NP_000509. The remaining 95% of the SNPs for prediction in which a variant could be detected, would have been sufficient in these cartoons, however may be misleading.  These results suggest that e.g. the introns (PMID: 11860449) or the entire Hb-beta locus may be  missing in beta(0) or be impeded ( O(2)-affinities) in Hb SS anemia beta-thalassemia and if so, α-thalassemia or Beta (gamma-beta-Thalassaemia and (Sickle Cell SCD-Hemoglobin)  Hb SS anemia, sickle cell disease.

A DNA-binding protein GATA1 with a biological unit FOG1 Zinc finger Protein molecule is ‘synergistic’ to the region of the X chromosome which occurred at a exome splice site X-linked involving the GATA-type zinc finger domain.

The human ERYF1 gene (summary) NF-E1 DNA-binding protein GATA1, locus Xp11.23 [§§] containing 2 ‘finger’ motifs referred to as ERYF1 of an erythroid-specific gene. The cDNA for the human ERYF1 gene is almost identical to that of chicken and mouse GATA1 gene consisting of 2 zinc finger’ type motifs its activator domain contains the binding sites for protein GATA1 and the CACCC (HS2)^ region. FOG is specific to this complex corresponding cDNA and interacts with element in the beta-globin IVS2 promoter from hemoglobin protein subunit promoters (alpha-chain gene‡, gamma, epsilon^ and  (embryonic), a switch from fetal to adult haemoglobin -or- relative to the T to C substitution of fetal hemoglobin (HPFH), implications for fetal hemoglobin – HbF“) distinct for erythroid (INHBA) and megakaryocyte differentiation, in vertabrate though, the N- and C-terminal thirds of the human protein.  Friend of GATA-1, FOG1; ZFPM1, zinc finger protein region a coregulator of the GATA1 associations facilitates a chromatin  locus control region(LCR)modifying proximity fetal to adult (gamma) to beta globin including the erythroid (EKLF krüpple-like) factor DNAse1^ histone  hypersensativesite (HS)^ locus (LCR) GATA1 establishes, facilitates interactions with immunoprecipitation, cross-regulatory roles reduced histone, acetylation and antagonism (EKLF-FlI-1) mechanisms. PU.1 – of the Ets family is ‘synergistic‘ to the major basic protein, (MBP) handles bistability in the erythroid-‘myeloid switch « directed by PU.1,’ influenced DNA binding and is  involved with MZF-1 (myeloid zinc finger 1), it interacts with the ‘C-terminal zinc finger « (CF)’ of GATA1. A bipotential function in multiple contexts (erythroid versusmegakaryocytic myeloid cells, GATA1 switches myeloid cell fate into eosinophils)° as two multi-protein complexes when segregated into two types (factor P-TEFb) one of the characteristics of (TAL-1, T-cell acute-) leukemic (SCL) stem cells is both types in circulating blood, for both the downregulation of GATA-1 and with the upregulation of GATA-2 (3q21)° that CD34␠ has the transcription capacity observed in immature hematopoietic progenitor stem cells, specific regions of each (Sequencing of FOG1 with GATA1 and GATA2), requires intact DNA-binding domains.  The C-terminal zinc finger (CF) basic tail shares, in an antagonistic fashion ‘mutations‘ in exon 2‡ (-GATA1s is a shorter GATA1 isoform (sf) found in DS (Down syndrome) a transient leukemia (TL)-AMKL) that lacks the transactivation‘” domain, in cis-acting GATA element, identification requires intact long forms (lf) of NF-E1 DNA-binding domain. Two novel zinc-finger domains demonstrate that the NFE1 gene cDNA-binding protein is assigned the human locus located in Xp11.23, required for normal megakaryocytic and erythroid development. A mutation in the FOG1-GATA1 N-terminal zinc finger (N-finger of leukemic cell (Igs)-immunoglobulins) or lacking the N-terminal activation the binding of Fog1 and the N-finger in the DNA face of Fog1, with non X-linked associations (16q2224) if different clinical entities linking to X-linked (X is any amino acid, substitution in the DNA-binding (Nf) region) thrombocytopenia in males-(XLTT*’-GATA1) with anemia low platelet levels traces discernable steps as embryos with a defect in forming erythroid burst-forming units BFU-E ☞ (summary – of all DNA that is transcribed which occurred at a exome splice site), to Minimal residual disease MRD – (cancer, “preleukemia” – myeloproliferative disorder (TMD), myeloid leukaemia-AML, SCL° and megakaryocytic AMKL) the GATA1-HS2-modified vector allowed remission in blood component and heme (Protoporphyrinogen) at the seventh GATA site in exon 1*’/intron-7° as a cofactor involving 6 non-coding exons and transactivation by USF1 and GATA1. A DNA Cytosine mechanism ara-c (Arabinofuranosylcytosine) short (sf) and (lf) long forms is used to kill these megakaryocytic cancer cells; clarifies that GATA-1 controls genes that manipulate the cell cycle and apoptotic cell death underlying normal (PI3K) and pathologic (PU.1) erythropoiesis – ‘differentiation’ is (FKBP12) lacking basal expression‘” in contrast to Bcl when Bcl-X(L) is cleaved by caspases. Anti-apoptotic Hsp70 protects GATA-1 during the switchingª of the erythroleukemia␠ cells that fail to complete maturation, proteolysis undergoing cell death in both the megakaryocytic and erythroid cells, established that phospholipase C (PLC)ª is involved in the signalling pathway(PI3K)/Akt equally expressed ‘as’ a probable negative FOG regulator, interacts with the PU.1 related Ets domain of  glycoprotein (GP)(1) VI*’ by expressing thrombopoietin activation of platelets in megakaryocytic cell lines, expressing both Fli-1 and GATA-1. A weak loss of aspartate in the amino-N-terminal zinc finger (Nf) loop GATA1’s three base substitution mutations results in incomplete megakaryocyte/platelet maturation as assessed by the DNA demethylating agent 5-azacytidine, activity in the presence of ara-c which occurred at a exome splice site. GATA1 appears to interact with RNA-mediated basal expression against these pathways, associated protein or mammalian targetsclarified that the basal transcription apparatus with transcription factors“ appears to interact with an HS2 region mutated in its GATA motif GATA1s a shorter GATA1 isoform.  

sequence [AT]GATA[AG] upper left 4 Angstroms of PDB 1GAT in this 4 Angstrom PDB 3VD6 r
Figure 1: PDB 1y0j-a  (MMDB ID: 31470; Mus musculus A). superimposed on -3vd6 4 Angstrons ogf DNA, six finger Znf DNA potential (‘X is any amino acid, substitution’) to co-ordinate C2H2 znf-1y0j-B (Protein chain B, MMDB ID: 31470), and the original structure of DNA_GATA1_HUMAN PDB: 1Y0J_uniprot/P15976 ProteinModelPortal P15976. / PDB: _3vd6; Names: GATA1 :ERYF1, GF1 with the consensus seqence [AT]GATA[AG] upper left DNA fragment seen in SPNA1  DNA binding  an essential determinant of specific GATA 1 Fig.2 binding, wraps around into the minor groove seen as the lower RNA representing PDB 1GAT in this single PDB 3VD6 rendering with PDB: 1YOJ- element-A DNA-binding protein GATA1 RNA Mus musculus eg. the red tail is the assumed Adjacent GATA DNA binding of PDB: 3DFV (Structure|id=PIRSF003027) Figure 2: 4 Angstroms of PDB 1GAT in this 4 Angstrom PDB 3VD6 rendering of 1YOJ-A RNA, modifyed to complete Fig.1. both are manually defined selected to provide The two zinc fingers functionality that contains 2 GATA-type zinc fingers (See; Figure 3: FOG1_B Zinc finger Protein (MMDB ID: 31470) has an absence of the PDB: 1YOJ- element- A DNA-binding protein GATA1 RNA thereby The two (Znf) fingers are functionally distinct bridging two separate DNA fragments (Structure|ids=PIRSF003027).
gata1 biological unit ara-C (Arabinofuranosylcytosine) Cytarabine (CID_6253; SDF File (.sdf)) = ara-c (MMDB ID: 23600 PDB ID: 1P5Z) Swiss PDB-viewer SPDBV
Figure 3: This incorporates PDB 1YOJ_A_B the Sructural basis of GATA1_A erythroid trascription factor and FOG1_B Zinc finger Protein (MMDB ID: 31470; Mus musculus A- Drosophila melanogaster-B) interactions with Human components of  Complexed With a molecue biological unit ara-C (Arabinofuranosylcytosine) Cytarabine (CID_6253; SDF File (.sdf)) = ara-c (MMDB ID: 23600 PDB ID: 1P5Z) short (sf) and (lf) long forms  2 ‘finger’ motifs of GATA 1 (lf) and FOG (sf) with  (FKBP12) basal expression PDB 2FAP_component A represented as the ligand surface partially framing the FOG heterodimer prevents formation of DNA component PDB: 1GAT-cDNA when lacking basal expression. This apparatus appears to interact with an HS2 region mutated in its GATA motif.
Zinc fingers as protein recognition motifs: structural basis for the GATA-1/Friend of GATA interaction 

Rendered with Swiss PDB-viewer SPDBV
about a horizontal axis of the Structures Image in the plane of the page
Mol Cell Biol. 2005 Feb;25(4):1215-27.
GATA1 function, a paradigm for transcription factors in hematopoiesis.
Swiss-pdb viewer software (

Spectrin alpha, erythrocytic 1 isoform GATA1 strand B cDNA containing the EF hand domain of P17678- GATA3 and a heterodimer assembly complexed with transmembrane SCF neural cell (Slc4a1) band 3 aspect of the alpha complex analogue Spna1.

SPNA1 PDB:1OWA Protein PDB: 1HYN Band 3, and GATA1 DNA strand B PDB:1GAT Spectrin alpha, erythrocytic 1 [ Mus musculus ] [§§; , ‡] anchored to the cytoplasmic face of the plasma membrane via ankyrin, which binds to beta-spectrin and is  affecting the conversion of spectrin dimers to tetramers erythroid alpha- or beta-spectrinRetrotransposon long terminal repeat 3′ LTR alpha 1 and the 5′ LTR alpha 2 gene sequence GATA factor,  cDNA contributes one strand a single gene that encodes the alpha-subunit limiting the lateral mobility of overall membrane glycolytic enzymes (GE) or membrane glycoproteins available to significantly modulate hemoglobin (Hb) in erythroid cells, mediates the binding of the whole complex to a transmembrane protein ubiquitous neural band 3, (Slc4a1) performs the same functions as that of erythroid glycolytic multienzyme (GE) complexes on band 3 via mRNAs for (Ank1) erythroid ankyrin and the function of various isoforms. Band 3 deficiency is used to characterize the alpha-chain and the Actin binding in proteins containing the EF hand domain and the non-erythroid analogue Spnb2 beta-spectrin (erythroid spectrin-like fodrin protein) subunits, cellular differentiation in erythroid alpha-spectrin mRNA alpha-globin region 3′-UTR aspect of the alpha complex. And the retention of DNase I-sensitive active sites within the human alpha-globin† (SCF) complex information on M-phase in mitotic chromosomes cell nucleus which divides genetically into two identical cells through cell division during Cellular differentiation in Embryonic Stem (ES) cells in fact, all erythroid (RBC) cell-specific genes have a WGATAR sequence to DNA at the consensus motifs. Erythroid iron assimilation, intestinal iron transport and erythroid iron utilization are the mechanisms necessary for (homeostasis) normal erythroid cells in Hemoglobin, or normoblastosis compared to iron deficiency anemia and linked to induction loci (spherocytosis and jaundice) induced erythroid burst formation (BFU-E) of a mouse Hemoglobin deficit (hbd) erythroleukemiaPU.1 bears a resemblance to  hemopoietic progenitors CFU-E/CFU-GM, and an ‘RNA element’ found during hemopoietic stem cell factor (SCF) development inhibits the erythroid program regulating the switch-of-fetal to adult† hemoglobin by binding to GATA-1 motifs and the CACCC-binding motif were essential for activity, and inhibit the DNA-binding activities of each other^, in Epo the erythroid ‘burst-forming system (BFU-E)’ that recruit increased proliferation of early erythroid cells, which lead to ‘erythropoietin-independent‘ erythropoiesis. Permanent cell lines can be established. And unlike the suggested following scheme of CBP also coimmunoprecipitate from spectrin alpha, erythrocytic 1. The erythroid specific  D-Aminolevulinic acid (ALA) synthase gene specifies an erythroid-specific mitochondrially located biosynthesis of the porphyrin heme cofactor, the NF-E2 gene is essential for globin transcription, alpha and the region of the human Beta globin (beta IVS2) are more common forms of the protein hemoglobin, in most red blood cells (RBC) derived from haematopoietic stem cells (SCF). There are two† forms, the latter newly formed erythrocytes, known as reticulocytes these induce mitochondrial autophagy, cell degradation of cellular components. Early erythroid progenitors [BFU-Es] stage express in blood volume some erythropoietin receptor (EpoR)  in the presence of only erythropoietin (Epo) induces ‘increased‘ signals for erythroid differentiation.  When epsilon-globin is no longer expressed Hematopoietic embryo stem cells (HSCs) can than be identified as [BFU-Es] murine erythroid progenitors in the CFU-E Myeloid stage, an assay derivative of the term syngeneic cell-lines^ in the hematopoietic stem cells colonies and lineages these functions perform to predict the mechanism that modulates erythrocyte alpha-spectrin and the function of various isoforms that comprise this gene however, supports up or downstream of this site the study of numerous molecular regulating mechanisms.

Spnb2 protein family architecture perspective and differences in complex form of exon/intron usage

Figure 3: Spnb2 instances of intron/exon usageSpectrin isoforms are found in erythroid and nonerythroid cells. Spectrin is a component (known as the postsynaptic density (PSD)) for the maintenance of cell  cytoskeleton shape  the main fibrous component of which is spectrin of the erythrocyte membrane controlling Smad3/4 subcellular localization in TGFβ/Smad signalling resulting in nuclear translocation  of activated Smad4. Nonerythroid brain spectrin (Spnb-2 Beta-II spectrin), Elf, embryonic liver beta-fodrin, are a stem cell adaptor protein, [§§; , ] )  or beta- fodrin (gene band 2p21, SPTAN1betaSpIIsigmaI) produces the amino-terminal fragment of the erythroid, beta subunit-fodrin, spectrin-like protein, is a nonerythroid spectrin analogue alpha Spna-1 related to human erythrocytic 1 (hSPTBN1). Beta-fodrin was  detected primarily at the apical membrane of epithelia, Spnb-2 binds only to N-CAM180 with reduced lateral mobility, E-cadherin-beta-catenin complexes is required to form the first cytoplasmic lateral membrane. Three isoforms of brain spectrin contains three structural domains, a cellular and dendritic isoform, 240/235– erythroid (RBCs) beta-spectrin cDNA- Complementary DNA synthesized from a messenger mRNA*,  contains a PH domain  that interact extensively with Phosphoinositides (PtdIns) of inositol 1,4,5-trisphosphate and receptor where the synapse phosphoproteome is functionally organized) binds with a nonerythroid 9 Kb mRNA which encodes neuronal beta SpIIa occurs also in neonatal cardiomyocytes with ankyrin-B and ELF  (Spnb-2), a new isoform of  beta-G-spectrin  or any spectrin-ankyrin to cross-react with human erythrocyte beta subunit spectrin-ankyrin scaffold in restoring similarity of structure to lateral membrane biogenesis. (Spnb2) represents a nonerythroid beta-spectrin subunit alphaI-(SH3) domain (human chromosome 10p11.2 — p12.) 235-E and A,  cellular and axonal neuron isoform, but not dendrites; and an isoform specific for astrocytes. ELF, is a TGF-beta1 adaptor and signaling molecule, and transform cells similar to RB protein*. Erythrocyte spectrin Elf -3 (Spnb-2) and apical to luminal stem cell peripheral blood T cell differentiation protein successfully manipulate mouse brain beta-G-spectrin with two known genes encoding the actin-cross-linking protein alphachain, and the Actin binding N-terminal domain of beta-chain a form of exon/intron usage of two antiparallel dimers. Spectrin contains an Src homology 3 (SH3) domain and share multiple exons by correlation to a known amino acid sequence of human brain beta-fodrin (hSPTBN1, gene ID 6711) .
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Human TGF-beta Type II Receptor

human TbetaR2 ectodomain--TGF-beta3 complex with ELF-3DNATGFBR type II receptors (TGFBR2) are transmembrane tyrosine kinases or associated with cytoplasmic tyrosine kinases** related to resistance to TGF-beta inhibition of cell proliferation and trap TGF-beta I from access to wild-type receptors, the growth-inhibitory and proapoptotic activities of the cytokine, human chromosome 3p22-p21: [§§; , ]. A cysteinerich wildtypeº SNP-(ancestral C-509T-allele and G-875A variant in TGFBR2) transition (exon 4) not an active mutation in the (constitutional) cDNA extracellular domain transmembrane (ECM) receptors cyclin-dependent kinases (cdks)º also bindsº to TGFBR2. ACVR2 (activin) a GS domain** member of the type II  receptor family ligandbinding domain and TGFBR type II* receptor, and mutations in exon 3 the polyadenine tract (BAT-RII, replication error-RER(+) in exons 4 phenotype, and 10-ACRV2* have premature termination codons (PTCs)-mRNAs can be regulated by miRNAs (endogenous non-coding RNAs) this is a use for inhibitors that can target,  PTC siRNA the effect could silence proteins using any C-terminal such as the gene promotor 5’UTR, mainly in the 3’UTR of mRNA) »» alter the response relative to TGF-beta (a multimer) that inhibits epithelial cell growth, however TGF-beta2 differs in that it binds the TGF-betaR-II isoform restricted to cells of bonemarrow (EC ‘vectors’) endothelial cells; induction of growth inhibition «« (Morin (flavonol), mannosidase and an molecular Bortezomib PTK/STK characterisation of TβRI suggest a novel mechanism an etoposide Epigallocatechin E.gallate provided by a (G)8, by reaction provides an unusual, C/T allele PKC interaction (autophosphorylation)** that is better able than wild-typeº to induce a the Influenza virus to maintain 3d cohesion of delivery (EGCG) binds with the anti-cancer drug Bortezomib=PMID:17634290dual kinase cytoplasmic domain specificity soluble betaglycan the type III receptor acts as potent type IIº inhibitor) and the loss of transphosphorylation or constitutive activation of TGF-beta1 mediated (homozygous and heterozygous polymorphism (heteroduplexes)» functionally related tentative (MMP) involvement of «three major systems as the Marfan syndrome type II gene) growth control or hypophosphorylation.  The functional inactivation of the Germline (Adenoviral -mediated soluble vectors bind and transform cells similar to RB protein retinoblastoma)-gene product (a dominant negatively acting mutant TbetaRIIDN) regulated by TGFBR type II receptors polyadenine (A)(10) tract  can result in microsatellite instability (MSI) of the microsatellite mutator phenotype (MMP) as RER(+), for ‘replication errors’ exhibiting, somatic type I receptor hereditary mutations ETS transcription factors (Ewing sarcoma EWS and related peripheral ESE ELF3 (ESE1/ESX), ets transcription factor binds to the TGF-beta RII promoter. Autophosphorylationprimitive tumors, mononucleotide (MSI-H microsatellite instabilityhigh) hereditary TGFBR2 and BAX (G)8 mononucleotide mutation guanine/adenine (G/A) with cytosine/thymine ‘C/T’ colon tumors) a putative tumor suppressor gene mutations, epithelial-mesenchymal transition (EMT). ETS supression requires functional TGFBR2, truncated type II receptors dominant-negative mutants that selectively block type II receptor signaling to TGF-beta induction (cell proliferation and differentiation and type I receptors ECM production) by inducing the escape of cells from TGF-beta-mediated growth control in the TGFBR2 gene characterized by germline plus induces secondary somatic mutations. Once the presence of TGFBR2 mutator mechanisms for germline mutations are generated, links (soluble vectors) have a Elf3 ‘C-terminal’ DNA-binding ETS-related domain retroviral (CAT)-construct expressing microsatellite instability (MSI) related to DNA-mismatch repair (MMR proficient and deficiencies) sequences of « Three”’ specific small interfering RNAs (siRNAs)”’ mono-, di-, and tri-nucleotide repeat hypermutable sequences targets many mRNAs mainly in the 3’UTR”’ of mRNA at the poly(A)(10) tract MMR (MRC-1) deficiency, results in intestinal epithelial defects of genes known to be mutated, deoxycytidine (DCK) restores TGF-beta type II receptor (MMR ‘initiated’ Apc mutation) in many cancer cell lines.

Transforming growth factor beta 1

synthetic ideas receptor complex of 2 TGFBR1 molecules

TGFBR1 are transmembrane tyrosine kinases or associated with cytoplasmic tyrosine kinase TGF-β‘s » specificity with type II receptors activating type I receptors, has the pre-helix extension and its role in binding are present on the plasma membrane (cytoplasmic domain) both as monomers and homo- and hetero-oligomers chromosome 9q22.33. 6 : [§§; , ]. Activin receptor-like kinase 5 (ALK-5) is a TGF-beta type I receptor, activation of Type I and binding to the type II receptors (as well as Endoglin, ENG (p.A60E) may increase susceptibility to various types of cancer, or augmented (PtdIns3P) phosphorylation in (non-Smad signalling pathways) integrated ( syndecan 4) procontractile AJ interactions « in disease states.) are detected and blocked by a antiapoptotic TGFbeta1-neutralizing antibody (To understand the expressions of TGFBR1,) at the cell surface transducing the TGF-beta signal to the cytoplasm (where the SMAD proteins, phosphorylate where they interact with DNA and move into the nucleus) involved in type II cell-matrix interactions, ALK1 and ALK5** adherens junction (AJ) complex (more basal than TJs) display opposing functions… Both are: transmembrane serine / threonine kinase also known as activin-like kinase (ALK) V*, epithelial-to-mesenchymal transition (EMT) responses, BMP7 can counteract with down-regulation of “‘occludin for efficient TGF-beta-dependent ‘dissolution’ (E3-proteasome-mediated TbetaR-I〃 associated type II degradation and Smad7 inhibition)  during follicular development (where Smad expression is not regulated and TSC-22 is dependent on ~ can be attributed to Endoglin) from the plasma membranes tight junctions (TJ) protein*”‘ expression conducive to spermatozoa maturation and storage. (TGF-beta) signaling proceeds from the cell membrane to the nucleus, AAV (adenovirus)**-TGF-beta1^ gene transfer integration site 1 (allele-specific (C to; T) expression^ (germline** allele-specific expression ASE)) including growth differentiation factor-9 (GDF9 both at the protein and mRNA expression levels of TGF-beta1specificity) are regulated by members of TGF-beta, and activin*. TGF-beta binds to these receptor’s 17alpha-hydroxylase/17,20 lyase activity, ALK5 (TbetaRII) inhibitors* coexpression is mediated by the ALK5 receptor; TGF-beta induces BGN [biglycan] expression through (the Smad-activating function of〃)… ALK5〃• that varies** between tissues. There is a conserved aspartic acid residue, which is important for the catalytic activity (Note: the suggested PTK~probability, with two protein kinase signatures the type I and type II receptors, is close to 100%,) of the enzyme. TGFB1 regulates cell cycle progression; involves its binding to TGFBR2 and activation of TGFBR1. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules results in the phosphorylation and the activation. Ligand binding may be a natural ligand Immunophilins FKBP12␠ (where FKBP12 predominated in yeast specifically with » mutationally₮ activated TbetaR-I , (TRAP-1) can distinguish *the receptor from wild-type receptor) in response to transient (Variant alleles with the deletion of exon-1 designated 6A) expression of TGFBR-(type)-1*6A (rs11466445) there are  distinct (binding of Xlinked〃• inhibitor) receptor-initiated intracellular pathways that are found to occur also« which bind FK506␠ (Tacrolimus) immunosuppressive drugs – (PAI1; plasminogen activator inhibitor-1), by the levels of activated receptors required to maintain active intracellular messengers SMADs (SMAD2SMAD4) RNA-binding protein with multiple splicing (RBPMS) complex, however Smad3 partners subsequently translocated binds Smad7₮ to type I receptor (TGFbeta RI (ALK5)) that the effect is dependent on TGFB-induced transcription (rapidly activate TGFbeta/Smad signaling) in the cytoplasm shuttle into the nucleus through Smad proteins as primary intracellular mediators.


TITLE CRYSTAL STRUCTURE OF ACTIVIN RECEPTOR TYPE II KINASE DOMAIN TITLE 2 FROM HUMANACVR2B of type I and IB the major mRNA species found during reproductive development, type II and IIA structurally related activin receptors Locus: 3p22.2 : [§§; ] and activates its serine/threonine kinase type-2 receptor then phosphorylates and activates (required for extracellular ligand binding the myostatin* signaling pathway), ‘the type-1′ (BMPs)  via a different set of SMAD proteins. ‘BMPR-II‘ may be compensated by BMP utilization of Acvr2a and Acvr2b including (ALK) activin receptor-like kinase. BMP-activated Smads, a SMAD proteins receptor, in the embryonic development (Müllerian ducts (Left-right axis malformations)) and developmental condition (heterotaxy) by heterozygous mutation in the ACVR2B gene’s conserved bilobal architecture moiety (which is orally active in two in-vivo models) due to an interaction by adenine in the fully active form of (ActRIIB)  critical for proper left-right development at later gestations well into adulthood. TGF-beta type II receptor GDF-5 [Growth/differentiation factor-5] bound to different sets distinct from the effects of ACE-031* (a soluble form of activin type IIB receptor (ActR-IB activation can be mimicked by T206D mutation of Thr-206 to ‘aspartic acid’)), either activin receptor-like kinase 4 (ALK4), and interacts with a  relationship between inhibin and activin which is essential modulator for the ‘modifiers’ interaction. Activin-A and a ALK1 pathway increases apoptosis in lymphatic vessels, myostatin [MSTN] , also referred as growth and differentiation factor 8 (GDF-8)  like that of its homolog (GDF11) inhibited Osteogenic protein-1 (OP-1) also known as BMP6/7 via  ActR type II receptors.

FLRG (follistatin-related gene; 3)


figure 1 Follistatin/Osteonectin-like EGF domainFollistatin/Osteonectin-like EGF domain, the FSTL3 gene chromosome 19p13: [§§; , ]. FLRG (follistatin-related gene; 3) found to be stored in secretory granules of the cells, encodes contains 2 cysteine-rich secretory proteins functioning as a secreted glycoprotein once bound to 2 potential N-glycosylation sites an exon/intron domain structure both the activin domain its propeptide (WFIKKN2) of the C terminus and FSTL3 inhibited BMP2, it is related to the class 1-1 complex free inhibitor follistatin modules functioning as a 27 kD secreted glycoprotein involved in the TGFbeta-inducible expression of the FLRG gene, or by transfection with Smad protein effects on hematopoiesis during erythropoiesis, promoting the primary mechanism of action to bioneutralizeº activin for both follistatin (FS) and FS-like 3 (FSTL-3) modulation of activin (ActRIIs),  myostatin, and other TGF beta superfamily signaling and uniquely with phosphatidylinositol 3-kinase a hypothetical complex activity in pseudogeneº secretory function composed of a protein family of extracellular matrix-associated glycoproteins functioning as a secreted glycoprotein.

Myostatin as part of a latent complex in the vicinity of the (D) polymorphism MSTN

3hh2-(Myostatin) of known structure IPR008197 Whey_acidic_proteinMyostatin , also known as growth and differentiation factor 8 (GDF8) a TGF-beta family member is (an inhibitor of myogenesis) secreted into the plasma expressed in human skeletal muscle (expressed in many different muscles throughout the body) as a 12.5-kD propeptide and a 26-kD glycoprotein (myostatin-immunoreactive protein) a dimer (three exons and two introns) locus: 2q32.2 [§§; ^] and WFIKKN2 protein (WAP, follistatin/kazal, kunitz, immunoglobulin, and netrin domain (WFIKKN2) containing 2) binds mature GDF8/myostatin and myostatin propeptide WFIKKN1 the paralogue (functional overlap) of these proteins. Myostatin » decreases muscle mass*, Myostatin-binding protein FLRG Protein, 2p6a with the two neighboring molecules 2p6A 3hh2 and 3hh2a in the vicinity of the (D) polymorphism MSTN of the consensus motiffollistatin-related gene « (15 g whey) via signals originating from the gut (e.g., GIP), increased mRNA muscle cell  (anabolicstimulus*) proliferation and differentiation, adipogenesis is blocked by RNAi silencing of signal to Wnt/beta-catenin/TCF4 pathway muscle and adipose tissue develop from the same mesenchymal stem cells. Synthesized (removed by subtilisin-like proprotein convertases (SPCs)) is the biologically active portion of the protein that hSGT (human small glutamine-rich tetratricopeptide repeat-containing protein) may play a role in regulation, and complexes with amyloid-beta like signal sequence. Myostatin circulates as part of a latent complex containing follistatin-related gene FLRG. Activin type II receptors (ActRIIs) transmit the activin-binding protein (FLRG) a protein that binds and inhibits activin*, the polymorphisms, showed their relation to – left » ventricular mass (LVM) – of endurance, acitvin receptor type « ACVRIIB and the myostatin propeptide is known to bind and inhibit myostatin in vitro.


English: Structure of protein GLP1R.Based on P...

English: Structure of protein GLP1R.Based on PyMOL rendering of PDB 3C59 . (Photo credit: Wikipedia)

Figure:1_Crystal Structure Of Glucagon-Like Peptide-1 In Complex With The Extracellular Domain Of The Glucagon-Like Peptide-1 Receptor_Figure:3 & 4GLP1 receptor (GLP1R) a seven-transmembrane family B G protein-coupled receptor (GPCR) locus : 6p21.2 [§§; ^], with a N-terminal extracellular domain is a potent insulinotropic incretin hormone important in maintaining blood glucose homeostasis, through their receptors, GLP1R and glucose-dependent insulinotropic polypeptide GIPR. The glucagon-like peptide-1 (GLP-1) C-terminal regions bind to the N terminus (NTD) this region of interaction is  mediated by the nGLP1R (receptor variants) released from the gut as an incretin  and oxyntomodulin (OXM) and DPP-IV inhibitors are structurally related gastrointestinal hormone secreted from enteroendocrine L cells into the blood stream governed by the tethered (beta)arr2. GLP-1R and the GIP receptor (GIP-R) affect the (liganddependent signal bias of extracellular loop-ECL2 mutations) pharmacological properties  (exendin-4  (from the venom of the lizard Heloderma suspectum) is used in humans, as a therapeutic tool: liraglutide) of these proteins, is neuroprotective. GLP1 and GLP1R are expressed in the brain and associated mechanisms in the central nervous system, regulation of neuroendocrine and behavioural responses in certain cells in the brain. TCF7L2 and GLP1R/GIPR expression effects on beta-cell function was decreased in human T2DM islets is a characteristic feature of NIDDM. GLP-1 stimulate secretion of pituitary hormones. GLP1 is a hormone derived from the preproglucagon molecule (GCG). GLP1 a Glucagon Receptor Antagonist dose not bind peptides of related structure glucagon, (GCG) does not modify (Unrelated, non-diabetic Pima Indians) the growth or apoptosis of a seven transmembrane (TM) domain protein (GLP1) in normal human pancreas ectopic expression of the pancreatic master regulator PDX-1* (pancreatic and duodenal homeobox gene 1) neuroendocrine transdifferentiation* of pancreatic ductal cells within the endocrine pancreas. The activity of this receptor is mediated by G proteins which activate adenylyl cyclaseADCY8  (brain) plays a central role including signalling via the GLP1R.

TCL7L2 traits and activity that affect its expression

TCL7L2 transcription factor 7-like 2 (T-cell specific, HMG-box) Ribbon diagram showing the overlay (CTNNB1 NCBI.pdbTCL7L2 Transcription factor 7-like 2 acts through regulation of proglucagon (GLP-1R) in enteroendocrine cells implicated in blood glucose homeostasis also called TCF4 of the four members of the downstream effector of Wnt signaling T-cell factor (TCF ) to human chromosome band 10q25.2, 25.3 : [§§; ^].  Noninsulin-dependent, susceptibality to TCF7L2, IVS3, CT  polymorphisms* (and high-risk rs7903146 TT genotype and low-risk CC genotype) to the ancestral T allele, excess androgen DNA binding domain (DBD),  PCOS-specific traits and activity (The TCF7L2 allele rs 7903146 ºª associated with impaired incretin signaling is modified by use of aspirin / NSAIDs; rs 290487 risk allele rs12255372* ‘ ºª  (associated with Pima Indians) and rs 10885409)  in intron 3, STRDG10S478 is located in islet-selective open chromatin within a 92-kb intron 4 block of Figure (2.) TCF4 with 2LEF DNA oriefted to figure (1.) Crystal Structure Of A Human Tcf-4 BETA-Catenin Complexlinkage disequilibrium population-attributable risk of 21% respectively for regulatory defects, of the TCF7L2 gene, comprises 17 exons, an intron can influence islet function,  on exons 1 and 2 cis-acting† binding extracellular ectodomain elements through the beta-catenin / E(epithelial)-cadherin pathway (GLCE† glucuronic acid epimerase: intestinal postprandial in both differentiation, undifferentiated states) lacking (CTBP-C-terminal* binding site) the essential function of the kinase activity in Wnt-TCF / beta-cateninbinding domain. That hypoxia inducible factor-1alpha (HIF-1a ) TCF1, and LEF1 contain a virtually identical N-terminal HMG box, numerous alternative splicings at its 3′ end* affect its expression. TCF1-alpha mediated gene transcription (beta-catenin) CTNNB1-N-terminal binding domain competes with TCF-4 for direct binding to beta-catenin DNA topoisomerase IIalpha (Topo IIalpha) inhibitors, merbarone and etoposide are component’s. Followed by in the absence of Wnt ligands a Groucho (TLE1)-interacting domain, the TCF4E harbors a C terminus, binding site. PKD1-polycystin transactivating factors include 4 TCF-binding elements (TBEs) due to the activation of beta-catenin/WNT signaling. A Tcf-4-binding element (TBE) in the COX-2 [cyclooxygenase-2] promoter may partly explain in colon and liver, carcinogenesis. In the absence of the Wnt signal, TCFs function as transcriptional repressors on the effects of myostatin (GDF8 the MSTN gene) on (TCF7L2) proliferation versus differentiation at TBE site 1.

CTNNB1 catenin (cadherin-associated protein), beta 1 and formation of branching point structures beta-catenin / LEF demonstrating nucleation at TBE1 site (TCF7L2)

Catenin Beta 1, CTNNB PDB:3FQR and the closely related T-cell factor 1 (TCF-1) Lymphoid enhancer-binding factor (PDB; 2LEF[-1]) as the technical DNA coil,Catenin Beta 1, CTNNB are cell adhesion molecules called (p120*catenin) cadherins (the (CDH1) E-cadherin/catenin complex) include the  beta-catenins a multifunctional molecule Locus: 3p22.1 [§§; ^]. Neurons also exhibited a higher CTNNB/TCF pathway association (concentration versus accumulation) with cadherins; CASchromosome segregation 1-like (yeast) binds with E-cadherin but not with beta-catenin. Which interacts with (Tcf-T-cell factor where a functional hypoxia switch is instigated, also coactivators, known as lymphocyte enhancer-binding factor, Lef) transcription factors “hot spots,” including 4 TCF-triple complex binding elements, (TBEs) express TCF4 (TCF7L2) polycystinPKD1 gene (pathophysiology∵) a target of the beta-catenin/TCF adhesion disruption pathway (proliferation versus differentiation, (1:1º) or cardiac left-right (LRº)ª asymmetry) at TBE1 site (TCF7L2). A minor nuclear-enriched monomeric form (ABC), or an alternative (Tcf1) isoform of « TCF-4,  outside of the canonical Wnt-regulated pathway from, conductin /Axin or functional differences acts as a scaffold upon part of a complex including (APC) adenomatous polyposis coli enhancing beta-catenin turnover as part of a protective mechanism. Alpha-catulin may associate with a beta-catenin fraction. In the absence of a Wnt signal, APC normally associates beta-catenin, the TCF7L2-PKD1∵ gene association is at the expense of sensory neuronal fate, this transcript does not include exon 1.  Virtually (in-vivo) all other (Wnt/beta-catenin) neural crest derivatives stabilizes beta-catenin / LEF and then upregulates downstream genes, cell-cell adhesion and Wnt-stimulated (transcriptional programmeª and { tumors arising from the Structure Of A<br />
Beta-Trcp1-Skp1-Beta-Catenin Complex: Destruction Motifurogenital tract} tumourigenesis. Phellinus linteus (PL) mushroom are (Herba Epimedii / 淫羊藿), known to possess anti-tumor effects through the inhibition of Wnt/β-catenin signaling for instance, the binding of b-cat to Tcf-4 was also disrupted by quercetin.) by mutations in the APC and beta-catenin genes transcriptional activation, TCF-/LEFmediated gene transcription (epithelial-mesenchymal transition (EMT)ª processes, in EC migrationº « (angiogenesis : anabolicº effects), cell-cell adhesion, and formation of branching point structures), in adherens junctions. AJs (AJAP1 might be one (TBE)) mediate adhesion between (beta-catenin has no nuclear localization signal) communicate a signal disruption and reestablishment to these cell to cell junctions (transit-amplifying (TA) preventing CTNNB1 from returning to the nucleus) to stop dividing and anchor the actin cytoskeleton serving the maintenance of epithelial layers in colonic epithelium layers (the intestinalª stem cell nicheº), such as organ lining surfacesª transactivates transcription with CTNNB giving heparan sulfate (HS) the ability to bind growth factors and cytokines. Junction plakoglobin (gamma-catenin) is among the three known plakophilins␠ a homologous  molecule  known as gamma-catenin or JUP found in a role in nucleating desmosomes of all epithelia, delta-catenin also demonstrated specific* high affinity binding. N-cadherin was associated with vinculin which serves a similar function as Alpha-catenin forms a 1:1º heterodimer with beta-catenin components of (AJ) adherens junctions that occur at cell–cell junctions.

LAR, Leukocyte common antigen related, Receptor-type tyrosine-protein phosphatase F (PTPRF)

PDB-1LAR Associated subunits RPTPs (receptor protein tyr. phos.) that acts as a protein-tyrosine phosphatase Domain 1The human LAR (PTPRF) gene has 2 tandemly repeated PTPase associated tandem subunit domains, locus: 1p34.2 [§§;^] and represents a receptor-type PTP (EC, through cell-cell or cellmatrix interactions processed into 2 noncovalently associated subunits RPTPs that acts as a protein-tyrosine phosphatase associate with Trk protein tyrosine kinase (PTK) receptors in the cytoplasmic segment for dephosphorylation of tyrosine-phosphorylated insulin receptor phosphorylated by insulin stimulation. LAR is a member of the PPFIA1 (liprin) family shown to interact with PTPRF.  PTP-LAR functional cell adhesion molecule (CAMs) domain 1 (cadherin and the cytoplasmic catenins) negatively regulates dephosphorylation in part of a complex (a region of the receptor-linked PTPases, absolutely required for LCA and LAR) of proteins (Trio/DAPK)placement of tyrosine phosphorylated 1LAR that is other wise in the center between the two domains D1 and D2 here on the D1 ribbon that constitute adherens junctions (AJs), the generally inactive (D2) extracellular cytoplasmic domain two  only decreases insulin receptor mediated autophosphorylation, a process called transcytosis. The PTPRF and CD45 molecule have both domains in the cytoplasmic segment. Trio (triple functional domain (PTPRF interacting)) contains three enzyme domains: 2 that forms a complex with the cytoplasmic segments of LAR protein and a cell adhesion-like ectodomain. LAR (PTPRF) is widely expressed in receptor-type protein-tyrosine-phosphatases as a regulator of insulin receptor (IR). Liprin localize LAR to cell focal adhesions-like ectodomain, the lamininnidogen complex is a ligand for a coiled-coil LAR-interacting protein where PPFIA1 co-localizes. LAR is important for dendrite development.

Protein-tyrosine phosphatase 1B

2CMC oriented towards pocket containing cysteine moleculePTPN1 nonreceptor type1 gene, which encodes PTP1B the prototypic member of the PTP family is responsible for negatively regulating insulin by dephosphorylating the phosphotyrosine (ptyr) residues* of the insulin receptor (INSR) kinase activation segment IRK (kinase domain of the insulin receptor) mainly by its association with IR localized to the plasma membrane in a Grb2 fashion, or by inhibiting insulin signaling locus: 20q13.1-q13.2 (EC, [§§] as well as JAK2 and TYK2 kinases. Leptin as well as insulin, induced the expression of PTP1B and T cell protein tyrosine phosphatase (TC-PTP) a closely related phosphatase. TYK2 and JAK2 are substrates, PTP1B expression augments STAM2 an RTK, phosphorylation downstream of JAK kinases. PTP-1B encoded by the PTPN1 gene and T-cellPTP localizes to the endoplasmic reticulum␠ oriented towards the cytoplasm (located on the cytosolic side of the endoplasmic reticulum post-translational C-terminal (The 1023(C)-common allele) attachment membrane anchor ») associated with microsomal membranes or an « interconnected network not ordinarily present in living cells with induction of the ER (endoplasmic reticulum)-stress response pharmacologically induced  (tunicamycin and thapsigargin) « in vitro » and in vivo, showing that suramin and vanadyl complexes a two-step mechanism reversibly mediated by the activation of PKA, that Ang II (Angiotensin) modulates, a group of blood-pressure-related phenotypes examine the catalytic domain of the apoenzymeand the effects of Astragalus membranaceus(黄芪) roots polysaccharide (APS). And competitive inhibitor of PTP1B and Yersinia PTP (YopH) contains all of the invariant residues present in human PTP1B including cysteine addition through a mechanism of inhibition (the catalytic loop) that CLK1 and CLK2 (CDC-like kinase) phosphorylate and activate enzymes in a perinuclear endosome compartment, and activate the S. cerevisiae PTP-1B family member YPTP1 Ran-gtpase activating protein, rangap1 in a dephosphorylated state (the inactive form) by PTP1B. N-cadherin binds PTP1B to  cell-to-cell variability, overexpression of hSPRY2 increases PTP1B without an increase in total* amount of cellular PTP1B to mediate cellular environment associated with PP2A activity, its eventual termination dephosphorylation and deactivation of insulin receptor substrate-1 the PTP1B-IRK interaction are unique to susceptibility. Secretion of insulin activates phosphoprotein phosphatase leading to dephosphorylation and enzymes reversibly mediated active at the same time, a biochemical pathway in which the liver generates glucose, Berberine(BBR) has recently been shown to improve insulin resistance. The 1484insG allele (mRNA) causes PTP1B overexpression at defined phosphotyrosine and RTK (receptor tyrosine kinase) sites, PTPases (TCPTP , PTP-LAR, Calcineurin) were cloned for N-terminal cDNA and included replacement of the C-terminal, the catalytic domains were identical to 40 PTPases receptor forms (“substrate-trappingmutants) and hepatic enzyme cofactors (genotyped in Pima Indians) in regulating glucose in liver, similar to the common leukocyte antigen CD45 (to exit the nucleus) and to leukocyte common antigen-related LAR in addition to the peptide sequence forms.

Non-receptor tyrosine-protein kinase TYK2

TYK2 bind phosphotyrosineTYK2 a Janus kinase, contains a C-terminal protein tyrosine kinase catalytic domain and has no Nterminal signal peptide or transmembrane domain, of coding regions of exons and the adjacent intronic DNA sequences, identical to tyk2 of mutant Tyk2 forms deleted at the N terminus locus:19p13.2 [§§], a human mRNA (rs2304256) exon¤ encoding a non-receptor protein tyrosine kinase, the Tyk2 deficiency is likely to account for the phenotype by preventing* Tyk2 tyrosine phosphorylation for interferon (IFN) responses and Stat activation. STAT1 and STAT3 translocated to the nucleus following PAF (platelet-activating factor) stimulation in the presence of TYK2 in controlling responses to multiple cytokines IFNAR1 (the Tyr-based endocytic motif within) or PLAUR (a UPA receptor) urokinase signaling complex uPA containing TYK2 and phosphatidylinositol 3-kinase PI3K stabilized at the cell surface are downstream events binding to the type I IFN TYK2 the DNA-binding domainreceptor complex a pathway that supplements ISGF3/interferon-stimulated response element, and IRF5 a regulator. (IFNaR1) domain (dimerized) is required to induce phosphorylation of binding helical bundled cytokines and TYK2 phenotypes ability at binding and signal transduction to the nucleus for the acquisition of DNA binding activity, and modulates uPAR dependent functional responses in upregulation of C5aR* expression. Mutations in TYK2 and STAT3 mostly impair IL-6R* responses, and polymorphisms¤. Phenylephrine induced tyrosine phosphorylation of Jak2, Tyk2, and STAT1. TYK2, has an SH2 domain that contains a histidine instead of arginine (semi- vs essential amino acid) it may have lost the ability on ligand-induced signaling to bind phosphotyrosine at a neutral pH of 7. Either of the two Src homology 2(SH2)p85 domains binds the pseudokinase domain (a hypothetical masking complex) of TYK2 directly.

TYK2 of 3NZO coding regions of exons and the adjacent intronic DNA

STAT1 signal transducer and activator of transcription 1

Two dimer interfaces are seen aligned termed antiparallel or parallel 1bf5 & 1yvl

antiparallel and parallel 1bf5 &1yvl aligned are seen

The JAK/STAT pathway signal transducer and activator of transcription STAT1 location: 2q32.2: [§§], is downstream of cytokine receptor IL2RG consisting of an N-terminal oligomerization domain surrounds a completely conserved arginine residue. And a C-terminal SRC homology-2 (SH2) domain and receptors which translocates GAF and  p48 ((protein 48), ISGF3) to the nucleus and upregulates in signal transduction from both the type I and type II interferons transcription of IFNG-regulated genes and protein inhibitor of the latent cytoplasmic transcription factor activated STAT1 PIAS1 (protein inhibitor of activated STAT1) interaction. Homeostatic balance antigen-driven proinflammatory chemokines and cytokine immune responses, are linked to a form of X-linked susceptibility, Nmi interacts with all STATs except Stat2, the (Stat) gene family has been highly conserved throughout evolution. Inherited impairment of the STAT1-dependent response to human IFNalpha/betaenvironment between STAT1 and the protein kinase doubleTyr701 transmigration route Via 74.56stranded RNA, are a double point mutation, microRNAs suppressed virus-associated double-stranded RNA. Saccharomyces cerevisiae, control STAT1 mRNA nuclear content that PIAS proteins promote, the nuclear pore-targeting of proteins that translocate into the nucleus and activate transcription in complex with mRNA (V: (−)ssRNA viruses, in a form deficient in DNA binding, enabling viruses to target– a Stat1 heterodimer, which lacks p48 a repressor region) to mycobacterial disease (disseminated BCG infection or vaccinated BCG locus: 2q32-37) that results in TYK2  Tyr701 note the two orange ** tags deficiency; in viral infection or other unidentified defects. ISGF3 binds to ISRE (interferon – stimulated response element) where they (STAT proteins) and their differences in IFN responsiveness (inducing a cell-mediated immunity) either act to or directly bind to DNA via signal transduction and activation of transcription after IFNG stimulation. STAT3 location: 17q21.2 is not activated by IFN-gamma but component p91 (IFN)-stimulated gene factor-3 known to be activated by JAKs the Janus kinases, which couple ligands IGF, IL6 and LIF dependent on the gp130-like leptin receptor (Obr) isoform, Stat3 gene C-terminal loop of the SH2 domain produced a molecule that dimerized (hetero- or homodimerize, and translocate to the nucleus) spontaneously, bound to DNA. Both signal transducer and activator of transcription factor 1 (STAT1) and STAT3 are activated in the liver.

antigen-driven proinflammatory immune responses in 'addition' contribute to

antigen-driven proinflammatory immune responses in ‘addition‘ contribute to: science has forced me to engineer medical attention 4  "idiotypic vaccines & humanized methods

Tyrosine-protein kinase JAK1

JAK1 PTK domain in complex with two JAK inhibitorsThe Janus kinase family, Type I and II cytokine receptors is immediately N-terminal to the PTK domain  1p31.3: [§§]. And JAK2 in the interferon-gamma pathway PTK activity is located in the C-terminal PTK‘-like domain has a negative role of an intrinsic JAK inhibitor suppressor of cytokine signaling (Cordyceps bassiana‘ may contain more than one active component as a multi-utility ethnomedicinal herbal) of a variable N-terminal region target sufficient for binding to a biotinylated* peptide on the cytokine receptor OSMR/gp130 and a C-terminal signaling cascade SOCS box of the OSMR box1/2 region. Suppressor Of Cytokine Signaling (SOCS) negatively regulate the Janus kinase, or inhibited enterovirus-induced signaling of JAK and activators of transcription (STAT) pathway, may be, the molecular site of action of taxifolin []. And myricetin could directly bind to JAK1/STAT3 molecules, these are the ‘softmolecular drug targets modality for immunosuppression. SOCS regulate JAK and EGFR signaling pathways, and LIF activated STAT of which SOCS-3 is a member and targeted IFN response factor 1- and class II transactivator-dependent and independent promoters, by suppressing the Janus**’* kinase-signal transducer ** and activator of transcription (JAK-STAT) pathway. Janus tyrosine kinase2 (TYK2), Jamip1 (Jak and microtubule interacting protein) associates via its C-terminal region activating multiple signaling (phosphorlration) pathways in parallel in HTLV-I infected T cells to facilitate* oncogenic transformation.  (JAK)-STAT cytokine-induced pathway proteins may influence GHR signalling other peripheral** effects*(the leptin (Ob) antiapoptotic effect, critical to both ‘innate’ and adaptive immunity), and in human liver, in NF‘-kappaB activation by IFN (alpha) and IFN-gamma cytokine receptor family along with subunit IFNGR by formation of inhibitory complexes subunit IFNAR binding to its specific cell surface receptor and activator of transcription, signal transducers and activators of transcription (STAT) pathway tyk, of STAT3 upstream kinases. JAK1 was stably associated with STAT3. IL-6 induces activation of JAK1 and JAK2 in human B cell lines. JAK/STAT signaling has been attributed to direct transcriptional regulation by STAT of specific target genes. Stat proteins are substrates of the Jak protein tyrosine kinases.

Oncostatin M a member of the IL-6 family of cytokines

Ribbon representation of oncostatin M showing ...

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Oncostatin M is a member of the IL-6 family of cytokines. OSM regulates the growth and differentiation of a number of tumor and normal cells. OSM, like LIF, is located on human chromosome 22, human OSM activates the LIF receptor heterodimer, containing defined regions of human chromosome 2q12.2: [§§]. OSM exclusively uses the OSMR* Oncostatin M receptor  composed of a binding subunit gp 130 heterodimer in signaling events related to leukaemia inhibitory factor (LIF) such as morphological changes upon soft agar colony formation. 4 molecules are structurally related to modulate differentiation of a variety of cell types to monocyte and from blood neutrophils and [À] Post-exercise infused *PMNs, C-terminal process functional changes induced by OSM (can hepcidin induce expression) to, endothelium along with basic epithelial tissues suggesting dedifferentiation of adipocytes, and  chondrocytes that OSM favors. gp130/OSMR is the only receptor complex to stimulate osteoprogenitor differentiation; binding to both gp130/LIFlow-affinity receptor beta  and gp130/OSM receptor beta heterocomplexes. Which trigger similar biological responses because they share gp130 as a common signal transducing transmembrane receptor. As well as cytolinkers induced by OSM, are inhibited by antibodies against gp130, the LDLR promoter (low density lipoprotein receptor)  repeat 3 sequence is identical to the repeats 1, 2, 3 TATA vector (pLDLR-R3) a cytokine-inducible immediate early gene promoter provides the C-terminal process where Egr1 may have a functional role in OM-induced upregulation of LDLR. The OM-responsive element that precedes and accompanies glycoprotein (gp)130 ligand family member cytokine OSM inhibitors. The gp130/OSMRbeta complex regulates PBEF and is activated by OSM only. Curcumin ((AP-1 inhibitor) diferuloylmethane), suppresses OSM-stimulated STAT1 phosphorylation, Piceatannol also inhibited OSM-induced VEGF mRNA expression. Forskolin induces OSM expression from outside the cell across the membrane to the inside of the cell. The combination of OSM and IL-1beta‘s functional effects Curcumin also inhibited within the CNS and synergy of other IL-6 family cytokines, production through a mechanism* (an inductor upregulated HGF [Hepatocyte growth factor] mRNA) requiring the synthesis or activation of a secondary mediating factor or as a pathway  utilized in various combinations with (bacterially expressed) hexameric ciliary neurotrophic factor (CNTF) . Anabolic growth factors can protect cartilage against OSM+TNF alpha induced destruction.  This effect is mediated by the transcription 3 (‘STAT 3’) binding to Parthenolide an OSM-responsive element.

The interleukin-6 signal transducer, gp130

Crystal structure of gp130 as published in the...

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The interleukin-6 signal transducer, gp130 the signal-transducing receptor chain of interleukin-6-type cytokines, IL6ST was assigned to chromosome 5q11.2: [§§], is a shared transducer chain triggered by homodimerization (IL6) on the plasma membrane IL-6-trans-signaling is counter balanced by a naturally occurring, soluble form of gp130 (sgp130) or heterodimerization with LIF-Rb/gp190 protein (IL11 has three distinct receptor binding sites, LIF, biologically active OSM or to ”type II” OSM receptor (OSMR/gp130), and CNTF) of gp130. Post-exercise infused PMNs, into situations such as minor subsequent muscle use latent hyperalgesia produced by the inflammogen, carrageenan (AgarAgar) can mediate inflammatory mediators of antisense for gp130 member of the ‘tall’ class of cytokine receptors including the conductor for gp130 signal transduction or a viral (vIL-6) transcriptional program or its capacity to respond to alloantigen or virally infected cells (or allogeneic cells is a profile consistent with the stimulation of proteoglycan (PG) release by OSM by an expansion in numbers of mature hematopoietic effector memory T lymphocytes or more primitive progenitors. It has been expected that evolutionary rate of genes is related negatively² (dealing with formal notations) with pleiotropy. IL-6 induced a rapid translocation of gp130 from the cell surface to endosomal compartments, and occurs via two distinct mechanisms in an autocrine manner via intracrine signaling of the two signal-transducing receptor subunits gp130 and LIFR complementary to those of the LIF site III-interactive proteins bind in a similar manner to that of growth hormone (site I and II) and can signal either as a homodimer or as a heterodimer, receptor-mediated interactions in this complex have not yet been fully resolved. LIFR explains why other gp130 binding cytokines do not act in synergy as OSM can signal through two separate heterodimeric receptor complexes to generate, respectively, type I and type II OSM receptor. The ‘extracellular region’ comprises six units of a fibronectin type III module consists of three extracellular domains several immunoglobulin-like and the third membrane the proximal fibronectin-like domain in the presence of soluble IL-6 receptor (sIL-6Rgp80). This type of signaling has been shown for hematopoietic progenitor cells, endothelial cells, and smooth muscle cells (are fundamentally different from skeletal muscle and cardiac muscle). The IL-6 receptor– complex differs from those of the receptor- complexes for LIF and OSM, gp130 is required. gp130 may also play a role in the nervous system as a cholinergic differentiation factor in nerve cells associated with dimerized but not monomeric gp130 of a pentameric receptor complex protein.  IL-11 acts on cells expressing gp130. CT-1 (cardiotrophin 1) activates gp130 transducing components determine the interaction with members of the Jak/STAT pathway Janus kinase family, gp130 preferentially activated STAT1 and STAT3, a consequence of imbalanced signals causes unexpected results.

Leukemia inhibitory factor LIF and the presence of other growth factors at the interface of a shared cell-surface signaling receptor.

LIF as prototypes (neurally active cytokine LIF), four helix bundle cytokines form, a functional receptor complexA protein variously termed leukemia inhibitory factor LIF locus : 22q12.2 [§§], exhibits pleiotropic biological activities, it plays a critical role in several endocrine functions including acting in synergy with other cytokines LIF and  BMP2 [2.] being in the centre of interest for doping abusers, equivalent to that observed in the presence of LIF alone and the presence of other growth factors. At the fetal-maternal interface on embryonic stem cells pluripotency to namely, extravillous cells of the anchoring villi induce astrocytes in cooperative signaling of LIF, and bone morphogenic proteins (BMP‘s) provides therapeutic targets to regulate ovarian function of the primordial follicles early in ovarian development and transition to the primary follicle [3.] at the maternalfetal interface signaling maintaining early pregnancy through Lif mediated in a paracrine way by uterine factors and in an autocrine way by trophoblastic factors. LIF is expressed early in human fetal pituitary development. LIF potently induces pituitary proopiomelanocortin (POMC) gene (HPA axis) hypothalamo-pituitary-adrenal axis transcription. LIF as prototypes for inhibitors targeting cytokin potently induces pituitary proopiomelanes (neurally active cytokine LIF), four helix bundle cytokines form, a functional receptor complex that act through a common heterodimeric* receptor composed of its receptor Lifr involved in binding the gp130 co-receptor on 3T3L1 cell extracts (bacterially expressed) at the interface of a shared cell-surface signaling receptor, (Glycoprotein 130) gp130dependent macrophage-mediated procoagulant function sensitive to hirudin and heparin-releasable mimetics induction of sympathetic substance P (SP) requires OSM, and  is structurally and functionally related to LIF. It induces a switch in neurotransmitter phenotype from adrenergic to cholinergic, identical to the signal transducing subunit of the IL-6 receptor, gp130 heterodimer* pathway, capable of binding this VIP reporter gene of the enteric nervous system induction and LIF activated STAT [1.] factors the Janus kinase-signal transducers and activators of transcription (Jak-Stat) via JAK2/STAT3 functional homodimer* pathway. (STAT) site of the promoter region induced by OSM and LIF activation, when mutated the hepcidin promoters several mutations (result in the development of anemia, and may play a role in the attraction of monocytes to the injured glomerulus) in hepcidins effect was markedly reduced, IL-4 and IL-10 cytokines have opposite effects (axotomy [4.] comparable to a retinoic acid responsive gene) on human pregnancy (IUGR), and preeclampsia (PE).  Oncostatin M (OSM) and and interleukin-6 are closely related cytokines, gp130 is required for signal transduction by these cytokines to which other subunits are added to modify ligand specificity. CNTF and LIF induce transcription of the VIP and other neuropeptide genes others appear to overlap and complement those of the neurotrophins.

FPR ligands a G protein-coupled receptor

The fMet-Leu-Phe (fMLP) receptor FMLP locus: 19q13.4 : [§§] or FPRL1 a mouse counterpart of FPRL1R (the peptide ligand Trp-Lys-Tyr-Met-Val-L-Met-NH(2) a synthetic peptide, WKYMVM uPAR epitope uPAR84-95, is an endogenous ligand for FPRL2 and FPRL1)  two closely related G-protein coupled receptors interact with viral and bacterial N-formyl peptides, peptides derived from the  N-terminal domain of annexin I serve as FPR ligands [3.]; a member of the GPCR family of receptors. A G protein-coupled receptor, receptors that are internalized in an arrestin-independent manner, that mediates phagocytic host cells to the invasion of microorganisms, N-formyl peptide receptor (FPR) is a key modulator of chemotaxis directing granulocytes toward sites of bacterial infections. T-cell-derived lymphokine human leukocyte inhibitory factor (LIF) is a modulator (PT (pertussis toxin) inhibits FMLP-mediated chemotaxis itself), of many important polymorphonuclear (PMN) functions results in an increase of the interleukin-8 (IL-8) mRNA accumulation and a subsequent release of the protein, and specific proinflammatory arachidonic acid (5-LO) product release, and FPRs colocalized with P2Y2 nucleotide receptors. Hypnotics and sedative drugs dose-dependently interfere with these activating pathways, TNF-mediated PMN oxidative priming may also promote oxidant tissue injury stimulated with the chemotactic peptide FMLP in whole blood originates, predominantly from neutrophils. Two chemoattractant receptor inhibitory proteins from Staphylococcus aureus blocks FPR and (FLIPr-SAB1019c, S. aureus-RF122) the     N-formylated peptide, an orphan G protein-coupled receptor while FPRL1-expressing cells migrated to picomolar concentrations of WKYMVm, also found (genistein [1.], staurosporin) inhibitor of protein kinase C (bis-indolyl-maleimide, BIM) was effective only in the cytolitic FMLP  and did not occur in PMN directly compare FPR levels specifically elicit exocytosis of gelatinase-rich [ch] and vitamin B-12 (secondary granules) binding protein-poor granules. FPR1 (formyl peptide receptor 1) may be the only receptor capable of binding prototype N-formyl peptides a key modulator of chemotaxis directing granulocytes toward sites of bacterial infections.

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MAL2 macrophage-activating lipopeptide 2

Desmodium yellow mottle virus Synthetic IDDLMAL2 macrophage-activating lipopeptide 2, TPD52 a coiled-coil motif-bearing protein and unrecognized prostate-specific protein, PrLZ (prostate leucine zipper), to which (toll-like receptor agonist macrophage-activating lipopeptide-2) MAL2 binds, is located on chromosome 8q21.13.; [§§]. (MALP-2) is essential for transcytosis across the interior of intestinal cells-bile canaliculus (basolateral to apical) membrane region, apically localized endosome structures en route to the canalicular surface, the process is also present elsewhere in a different compartment from that containing MAL in thyroid epithelial cells TPD52, to which MAL2s 4 transmembrane domain exons bind, M. fermentans total proteins, LPMf (fMetLeuPhe: isolated from bacterial filtrates origionally.) or MALP-2 (M. fermentans synthetic lipopeptide), RFLP pattern (restriction fragment length polymorphism) based on the distribution of an insertion element (IS1550) suggests in Gram-positive bacteria that human pathogen Mycoplasma fermentans (wall-less prokaryotes)  isolates possess inter-strain variation in the chemoattractant (FMLP) yet their identity is conserved as (RFLP) and have the ability to activate human peripheral blood monocytes in their interaction with B cells and surface capsular material, a cytocidal activity that does not apply to other mycoplasma species, mD52 vaccination induces an immune response. MALP-2 has been expressed at the surface of M. fermentans as a molecular entity sMALP-2. MAL2 colocalized in subapical endosome structures with transcytosing molecules (PIGR and CD59), en route to the apical surface where MAL2 resides selectively in raft protein of the MAL family.