| IED ID | IndEnz0018000506 |
| Enzyme Type ID | peroxidase000506 |
| Protein Name |
Hematopoietic prostaglandin D synthase H-PGDS EC 5.3.99.2 GST class-sigma Glutathione S-transferase EC 2.5.1.18 Glutathione-dependent PGD synthase Glutathione-requiring prostaglandin D synthase Prostaglandin-H2 D-isomerase |
| Gene Name | HPGDS GSTS PGDS PTGDS2 |
| 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 | MPNYKLTYFNMRGRAEIIRYIFAYLDIQYEDHRIEQADWPEIKSTLPFGKIPILEVDGLTLHQSLAIARYLTKNTDLAGNTEMEQCHVDAIVDTLDDFMSCFPWAEKKQDVKEQMFNELLTYNAPHLMQDLDTYLGGREWLIGNSVTWADFYWEICSTTLLVFKPDLLDNHPRLVTLRKKVQAIPAVANWIKRRPQTKL |
| Enzyme Length | 199 |
| Uniprot Accession Number | O60760 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: Prostaglandin PGD2 synthesis is stimulated by calcium and magnesium ions. One calcium or magnesium ion is bound between the subunits of the homodimer. The interactions with the protein are for the most part mediated via water molecules. Magnesium increases the affinity for glutathione, while calcium has no effect on the affinity for glutathione. {ECO:0000269|PubMed:12627223}. |
| Binding Site | BINDING 8; /note="Glutathione"; /evidence="ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825, ECO:0000269|PubMed:16547010, ECO:0000269|PubMed:18341273, ECO:0000269|PubMed:19939518"; BINDING 14; /note="Glutathione"; /evidence="ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825, ECO:0000269|PubMed:16547010, ECO:0000269|PubMed:18341273, ECO:0000269|PubMed:19939518"; BINDING 39; /note="Glutathione"; /evidence="ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825, ECO:0000269|PubMed:16547010, ECO:0000269|PubMed:18341273, ECO:0000269|PubMed:19939518" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=prostaglandin H2 = prostaglandin D2; Xref=Rhea:RHEA:10600, ChEBI:CHEBI:57405, ChEBI:CHEBI:57406; EC=5.3.99.2; Evidence={ECO:0000269|PubMed:10824118, ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:12244105, ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:16547010, ECO:0000269|PubMed:19939518, ECO:0000269|PubMed:9353279, ECO:0000269|PubMed:9425264};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10601; Evidence={ECO:0000305|PubMed:10824118, ECO:0000305|PubMed:12244105}; 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:10824118, ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:15113825}; CATALYTIC ACTIVITY: Reaction=2-glyceryl-prostaglandin H2 = 2-glyceryl-prostaglandin D2; Xref=Rhea:RHEA:51232, ChEBI:CHEBI:85166, ChEBI:CHEBI:133979; Evidence={ECO:0000269|PubMed:12244105};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51233; Evidence={ECO:0000305|PubMed:12244105}; |
| DNA Binding | |
| EC Number | 5.3.99.2; 2.5.1.18 |
| Enzyme Function | FUNCTION: Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range of aryl halides and organic isothiocyanates. Also exhibits low glutathione-peroxidase activity towards cumene hydroperoxide. {ECO:0000269|PubMed:10824118, ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:12244105, ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825, ECO:0000269|PubMed:16547010, ECO:0000269|PubMed:19939518, ECO:0000269|PubMed:9353279, ECO:0000269|PubMed:9425264}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (6); Binding site (3); Chain (1); Domain (2); Helix (13); Mutagenesis (3); Region (2); Sequence conflict (1); Turn (1) |
| Keywords | 3D-structure;Calcium;Cytoplasm;Fatty acid biosynthesis;Fatty acid metabolism;Isomerase;Lipid biosynthesis;Lipid metabolism;Magnesium;Metal-binding;Prostaglandin biosynthesis;Prostaglandin metabolism;Reference proteome;Transferase |
| Interact With | Q96GS6; Q96B67; P15018; P08582-2; Q13370; Q8N1H7 |
| Induction | INDUCTION: By 12-O-tetradecanoylphorbol-13-acetate (TPA). {ECO:0000269|PubMed:9425264}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9353279}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (30) |
| Cross Reference PDB | 1IYH; 1IYI; 1V40; 2CVD; 2VCQ; 2VCW; 2VCX; 2VCZ; 2VD0; 2VD1; 3EE2; 3KXO; 3VI5; 3VI7; 4EC0; 4EDY; 4EDZ; 4EE0; 5AIS; 5AIV; 5AIX; 5YWE; 5YWX; 5YX1; 6N4E; 6W58; 6W8H; 6ZTC; 7JR6; 7JR8; |
| Mapped Pubmed ID | 10329152; 10587441; 10783391; 11327815; 12002745; 12042665; 12211029; 12707014; 16081649; 16298388; 16548513; 18946232; 19124506; 19181746; 19247692; 19276290; 19913121; 20074808; 20083122; 20085333; 20628086; 21106529; 21668448; 21683347; 21821144; 22049022; 22418579; 22522127; 22546671; 24996417; 25416956; 25978964; 27145233; 27485270; 30121213; 30858025; 33059303; 33991628; 8182750; 8203914; 8331657; 8431482; 9551553; 9839448; |
| Motif | |
| Gene Encoded By | |
| Mass | 23,344 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=8 mM for glutathione for the glutathione-conjugating activity {ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825}; KM=0.6 mM for glutathione for the prostaglandin D synthase activity in the presence of EDTA {ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825}; KM=0.14 mM for glutathione for the prostaglandin D synthase activity in the presence of magnesium ions {ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825}; Vmax=8.6 umol/min/mg enzyme with 1-bromo-2,4-dinitrobenzene as substrate {ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825}; Vmax=5.1 umol/min/mg enzyme with 1-chloro-2,4-dinitrobenzene as substrate {ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825}; Vmax=44.3 umol/min/mg enzyme with 1-fluoro-2,4-dinitrobenzene as substrate {ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825}; Vmax=10.7 umol/min/mg enzyme with 1-iodo-2,4-dinitrobenzene as substrate {ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825}; Vmax=6.8 umol/min/mg enzyme with allyl isothiocyanate as substrate {ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825}; Vmax=6.3 umol/min/mg enzyme with benzyl isothiocyanate as substrate {ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825}; Vmax=0.05 umol/min/mg enzyme with cumene hydroperoxide as substrate {ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:12627223, ECO:0000269|PubMed:15113825}; |
| Metal Binding | |
| Rhea ID | RHEA:10600; RHEA:10601; RHEA:16437; RHEA:51232; RHEA:51233 |
| Cross Reference Brenda | 2.5.1.18;5.3.99.2; |