| IED ID | IndEnz0018000346 |
| Enzyme Type ID | peroxidase000346 |
| Protein Name |
Glutathione S-transferase A1 EC 2.5.1.18 13-hydroperoxyoctadecadienoate peroxidase EC 1.11.1.- Androst-5-ene-3,17-dione isomerase EC 5.3.3.- GST HA subunit 1 GST class-alpha member 1 GST-epsilon GSTA1-1 GTH1 Cleaved into: Glutathione S-transferase A1, N-terminally processed |
| Gene Name | GSTA1 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MAEKPKLHYFNARGRMESTRWLLAAAGVEFEEKFIKSAEDLDKLRNDGYLMFQQVPMVEIDGMKLVQTRAILNYIASKYNLYGKDIKERALIDMYIEGIADLGEMILLLPVCPPEEKDAKLALIKEKIKNRYFPAFEKVLKSHGQDYLVGNKLSRADIHLVELLYYVEELDSSLISSFPLLKALKTRISNLPTVKKFLQPGSPRKPPMDEKSLEEARKIFRF |
| Enzyme Length | 222 |
| Uniprot Accession Number | P08263 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: The isomerase activity is inhibited by S-methylglutathione (GSMe). {ECO:0000269|PubMed:11152686}. |
| Binding Site | BINDING 9; /note="Glutathione"; /evidence="ECO:0000269|PubMed:16421451, ECO:0000269|PubMed:19618965"; BINDING 45; /note="Glutathione"; /evidence="ECO:0000269|PubMed:16421451, ECO:0000269|PubMed:19618965" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=glutathione + RX = a halide anion + an S-substituted glutathione + H(+); Xref=Rhea:RHEA:16437, ChEBI:CHEBI:15378, ChEBI:CHEBI:16042, ChEBI:CHEBI:17792, ChEBI:CHEBI:57925, ChEBI:CHEBI:90779; EC=2.5.1.18; Evidence={ECO:0000269|PubMed:20606271};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16438; Evidence={ECO:0000305|PubMed:20606271}; CATALYTIC ACTIVITY: Reaction=glutathione + prostaglandin A2 = prostaglandin A2-S-(R)-glutathione; Xref=Rhea:RHEA:50796, ChEBI:CHEBI:57925, ChEBI:CHEBI:133370, ChEBI:CHEBI:133768; Evidence={ECO:0000269|PubMed:9084911};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50797; Evidence={ECO:0000305|PubMed:9084911}; CATALYTIC ACTIVITY: Reaction=glutathione + prostaglandin J2 = prostaglandin J2-S-(R)-glutathione; Xref=Rhea:RHEA:50804, ChEBI:CHEBI:57925, ChEBI:CHEBI:133396, ChEBI:CHEBI:133771; Evidence={ECO:0000269|PubMed:9084911};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50805; Evidence={ECO:0000305|PubMed:9084911}; CATALYTIC ACTIVITY: Reaction=(13S)-hydroperoxy-(9Z,11E)-octadecadienoate + 2 glutathione = (13S)-hydroxy-(9Z,11E)-octadecadienoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:48888, ChEBI:CHEBI:15377, ChEBI:CHEBI:57466, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:90850; Evidence={ECO:0000269|PubMed:16624487};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48889; Evidence={ECO:0000305|PubMed:16624487}; CATALYTIC ACTIVITY: Reaction=androst-5-ene-3,17-dione = androst-4-ene-3,17-dione; Xref=Rhea:RHEA:43936, ChEBI:CHEBI:16422, ChEBI:CHEBI:83865; Evidence={ECO:0000269|PubMed:11152686};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43937; Evidence={ECO:0000305|PubMed:11152686}; |
| DNA Binding | |
| EC Number | 2.5.1.18; 1.11.1.-; 5.3.3.- |
| Enzyme Function | FUNCTION: Glutathione S-transferase that catalyzes the nucleophilic attack of the sulfur atom of glutathione on the electrophilic groups of a wide range of exogenous and endogenous compounds (Probable). Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). It also catalyzes the isomerization of D5-androstene-3,17-dione (AD) into D4-androstene-3,17-dione and may therefore play an important role in hormone biosynthesis (PubMed:11152686). Through its glutathione-dependent peroxidase activity toward the fatty acid hydroperoxide (13S)-hydroperoxy-(9Z,11E)-octadecadienoate/13-HPODE it is also involved in the metabolism of oxidized linoleic acid (PubMed:16624487). {ECO:0000269|PubMed:11152686, ECO:0000269|PubMed:16624487, ECO:0000269|PubMed:9084911, ECO:0000305|PubMed:20606271}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8.0 for the isomerization of androst-5-ene-3,17-dione. {ECO:0000269|PubMed:11152686}; |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (5); Binding site (2); Chain (2); Domain (2); Helix (11); Initiator methionine (1); Modified residue (3); Mutagenesis (3); Natural variant (3); Region (2); Sequence conflict (5); Turn (2) |
| Keywords | 3D-structure;Acetylation;Cytoplasm;Direct protein sequencing;Isomerase;Lipid metabolism;Oxidoreductase;Peroxidase;Reference proteome;Transferase |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm. |
| Modified Residue | MOD_RES 1; /note="N-acetylmethionine"; /evidence="ECO:0000250|UniProtKB:P80894"; MOD_RES 2; /note="N-acetylalanine; in Glutathione S-transferase A1, N-terminally processed"; /evidence="ECO:0000250|UniProtKB:P30115"; MOD_RES 4; /note="N6-succinyllysine"; /evidence="ECO:0000250|UniProtKB:P30115" |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (35) |
| Cross Reference PDB | 1GSD; 1GSE; 1GSF; 1GUH; 1K3L; 1K3O; 1K3Y; 1LBK; 1PKW; 1PKZ; 1PL1; 1PL2; 1USB; 1XWG; 1YDK; 2R3X; 2R6K; 3I69; 3I6A; 3IK9; 3KTL; 3L0H; 3Q74; 3U6V; 3ZFB; 3ZFL; 4HJ2; 5JCU; 5LCZ; 5LD0; 6ATO; 6ATP; 6ATQ; 6ATR; 6YAW; |
| Mapped Pubmed ID | 10329152; 10587441; 10783391; 11327815; 11535243; 11550208; 11692074; 11747461; 11851347; 11931663; 12042665; 12087351; 12093480; 12139976; 12206662; 12234984; 12447480; 12473455; 12516103; 12524083; 12627223; 12871945; 14690442; 15128049; 15182170; 15202795; 15319294; 15525789; 15616829; 15746160; 15757902; 15797627; 15808404; 15900282; 15952767; 16081649; 16116487; 16190865; 16280386; 16298388; 16365014; 16548513; 16599007; 16624829; 16717136; 16786188; 16865249; 17021248; 17071629; 17086718; 17197702; 17333241; 17374652; 17425746; 17601350; 17631926; 17644396; 17716224; 17899366; 18065725; 18066575; 18161889; 18186040; 18214047; 18224491; 18300949; 18414193; 18430527; 18476723; 18496131; 18635758; 18641537; 18644106; 18784548; 18791061; 18854779; 18977241; 18992148; 19027952; 19062541; 19076156; 19273602; 19343046; 19376514; 19448608; 19491810; 19515364; 19584821; 19696793; 19786980; 19789190; 19896490; 19902075; 19953622; 19959275; 20032816; 20056632; 20083122; 20085333; 20100551; 20102361; 20200426; 20207535; 20216541; 20237496; 20331903; 20367187; 20368715; 20374258; 20377137; 20391138; 20437058; 20529827; 20672371; 20711500; 20833278; 21106529; 21163259; 21169260; 21530062; 21530499; 21668448; 21749698; 21844655; 21988832; 22002059; 22040239; 22079734; 22444596; 22475179; 22522127; 22633257; 22697302; 22893351; 22906494; 22959778; 22993865; 23251616; 23292236; 23394311; 23460799; 23570881; 23647087; 23650189; 23731957; 24075358; 24192117; 24215845; 24276031; 24344877; 24390679; 24423050; 24471578; 24612768; 24782212; 24914957; 24974183; 25111321; 25251951; 25374180; 25565670; 25730183; 25778330; 25867434; 26222310; 26321410; 26419450; 26691424; 27179909; 27449362; 27500405; 27568660; 27612661; 27631264; 27684484; 27936036; 28267438; 28401601; 28677395; 29087247; 29165597; 29959055; 30431119; 30963629; 30987408; 31834435; 32284348; 32822468; 33002252; 33658540; 33924269; 4980931; 6989049; 7372607; 8182750; 8203914; 9240432; 9551553; 9839448; |
| Motif | |
| Gene Encoded By | |
| Mass | 25,631 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=160 uM for prostaglandin A2 (at pH 7.0 and 37 degrees Celsius) {ECO:0000269|PubMed:9084911}; KM=160 uM for glutathione (at pH 8.0) {ECO:0000269|PubMed:11152686}; KM=58 uM for androst-5-ene-3,17-dione (at pH 8.0) {ECO:0000269|PubMed:11152686}; Vmax=121 nmol/min/mg enzyme for the formation of the glutathione-S-conjugate of prostaglandin A2 (at pH 7.0 and 37 degrees Celsius) {ECO:0000269|PubMed:9084911}; Vmax=40 umol/min/mg enzyme for the isomerization of androst-5-ene-3,17-dione (at pH 8.0) {ECO:0000269|PubMed:11152686}; Note=kcat is 29.3 sec(-1) for the isomerization of androst-5-ene-3,17-dione. {ECO:0000269|PubMed:11152686}; |
| Metal Binding | |
| Rhea ID | RHEA:16437; RHEA:16438; RHEA:50796; RHEA:50797; RHEA:50804; RHEA:50805; RHEA:48888; RHEA:48889; RHEA:43936; RHEA:43937 |
| Cross Reference Brenda | 2.5.1.18; |