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| | ==CRYSTAL STRUCTURE OF HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE COMPLEX WITH GLUTATHIONE== | | ==CRYSTAL STRUCTURE OF HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE COMPLEX WITH GLUTATHIONE== |
| - | <StructureSection load='1pd2' size='340' side='right' caption='[[1pd2]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='1pd2' size='340' side='right'caption='[[1pd2]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1pd2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PD2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PD2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1pd2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PD2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PD2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Prostaglandin-D_synthase Prostaglandin-D synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.99.2 5.3.99.2] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pd2 OCA], [http://pdbe.org/1pd2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1pd2 RCSB], [http://www.ebi.ac.uk/pdbsum/1pd2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1pd2 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1pd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pd2 OCA], [https://pdbe.org/1pd2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pd2 RCSB], [https://www.ebi.ac.uk/pdbsum/1pd2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pd2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HPGDS_RAT HPGDS_RAT]] 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.<ref>PMID:10871602</ref> <ref>PMID:11672424</ref> <ref>PMID:16547010</ref> <ref>PMID:9323136</ref> | + | [https://www.uniprot.org/uniprot/HPGDS_RAT HPGDS_RAT] 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.<ref>PMID:10871602</ref> <ref>PMID:11672424</ref> <ref>PMID:16547010</ref> <ref>PMID:9323136</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1pd2" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1pd2" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Prostaglandin-D synthase]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Ago, H]] | + | [[Category: Ago H]] |
| - | [[Category: Miyano, M]] | + | [[Category: Miyano M]] |
| - | [[Category: Gst]]
| + | |
| - | [[Category: Hematopoietic prostaglandin d synthase]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Pgd]]
| + | |
| - | [[Category: Sigma-class gst]]
| + | |
| Structural highlights
Function
HPGDS_RAT 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.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Hematopoietic prostaglandin (PG) D synthase is the key enzyme for production of the D and J series of prostanoids in the immune system and mast cells. We isolated a cDNA for the rat enzyme, crystallized the recombinant enzyme, and determined the three-dimensional structure of the enzyme complexed with glutathione at 2.3 A resolution. The enzyme is the first member of the sigma class glutathione S-transferase (GST) from vertebrates and possesses a prominent cleft as the active site, which is never seen among other members of the GST family. The unique 3-D architecture of the cleft leads to the putative substrate binding mode and its catalytic mechanism, responsible for the specific isomerization from PGH2 to PGD2.
Cloning and crystal structure of hematopoietic prostaglandin D synthase.,Kanaoka Y, Ago H, Inagaki E, Nanayama T, Miyano M, Kikuno R, Fujii Y, Eguchi N, Toh H, Urade Y, Hayaishi O Cell. 1997 Sep 19;90(6):1085-95. PMID:9323136[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pinzar E, Miyano M, Kanaoka Y, Urade Y, Hayaishi O. Structural basis of hematopoietic prostaglandin D synthase activity elucidated by site-directed mutagenesis. J Biol Chem. 2000 Oct 6;275(40):31239-44. PMID:10871602 doi:http://dx.doi.org/10.1074/jbc.M000750200
- ↑ Jowsey IR, Thomson AM, Flanagan JU, Murdock PR, Moore GB, Meyer DJ, Murphy GJ, Smith SA, Hayes JD. Mammalian class Sigma glutathione S-transferases: catalytic properties and tissue-specific expression of human and rat GSH-dependent prostaglandin D2 synthases. Biochem J. 2001 Nov 1;359(Pt 3):507-16. PMID:11672424
- ↑ Aritake K, Kado Y, Inoue T, Miyano M, Urade Y. Structural and functional characterization of HQL-79, an orally selective inhibitor of human hematopoietic prostaglandin D synthase. J Biol Chem. 2006 Jun 2;281(22):15277-86. Epub 2006 Mar 17. PMID:16547010 doi:10.1074/jbc.M506431200
- ↑ Kanaoka Y, Ago H, Inagaki E, Nanayama T, Miyano M, Kikuno R, Fujii Y, Eguchi N, Toh H, Urade Y, Hayaishi O. Cloning and crystal structure of hematopoietic prostaglandin D synthase. Cell. 1997 Sep 19;90(6):1085-95. PMID:9323136
- ↑ Kanaoka Y, Ago H, Inagaki E, Nanayama T, Miyano M, Kikuno R, Fujii Y, Eguchi N, Toh H, Urade Y, Hayaishi O. Cloning and crystal structure of hematopoietic prostaglandin D synthase. Cell. 1997 Sep 19;90(6):1085-95. PMID:9323136
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