5aiv
From Proteopedia
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| - | ''' | + | ==Complex of human hematopoietic prostagandin D2 synthase (hH-PGDS) in complex with an active site inhibitor.== |
| + | <StructureSection load='5aiv' size='340' side='right' caption='[[5aiv]], [[Resolution|resolution]] 2.04Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5aiv]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AIV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AIV 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>, <scene name='pdbligand=M1W:3-(1H-INDOL-4-YL)-N-(3-METHOXYPROPYL)-1,2,4-OXADIAZOLE-5-CARBOXAMIDE'>M1W</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ais|5ais]]</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=5aiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5aiv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5aiv RCSB], [http://www.ebi.ac.uk/pdbsum/5aiv PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/HPGDS_HUMAN HPGDS_HUMAN]] 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:10824118</ref> <ref>PMID:11672424</ref> <ref>PMID:9425264</ref> <ref>PMID:9353279</ref> <ref>PMID:12627223</ref> <ref>PMID:15113825</ref> <ref>PMID:16547010</ref> <ref>PMID:19939518</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human H-PGDS has shown promise as a potential target for anti-allergic and anti-inflammatory drugs. Here we describe the discovery of a novel class of indole inhibitors, identified through focused screening of 42,000 compounds and evaluated using a series of hit validation assays that included fluorescence polarization binding, 1D NMR, ITC and chromogenic enzymatic assays. Compounds with low nanomolar potency, favorable physico-chemical properties and inhibitory activity in human mast cells have been identified. In addition, our studies suggest that the active site of hH-PGDS can accommodate larger structural diversity than previously thought, such as the introduction of polar groups in the inner part of the binding pocket. | ||
| - | + | Identification of indole inhibitors of human hematopoietic prostaglandin D2 synthase (hH-PGDS).,Edfeldt F, Evenas J, Lepisto M, Ward A, Petersen J, Wissler L, Rohman M, Sivars U, Svensson K, Perry M, Feierberg I, Zhou XH, Hansson T, Narjes F Bioorg Med Chem Lett. 2015 Jun 15;25(12):2496-500. doi:, 10.1016/j.bmcl.2015.04.065. Epub 2015 Apr 28. PMID:25978964<ref>PMID:25978964</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Edfeldt, F]] | [[Category: Edfeldt, F]] | ||
| + | [[Category: Evenas, J]] | ||
| + | [[Category: Feierberg, I]] | ||
| + | [[Category: Hansson, T]] | ||
| + | [[Category: Lepisto, M]] | ||
| + | [[Category: Narjes, F]] | ||
[[Category: Perry, M]] | [[Category: Perry, M]] | ||
| - | [[Category: | + | [[Category: Petersen, J]] |
| + | [[Category: Rohman, M]] | ||
[[Category: Sivars, U]] | [[Category: Sivars, U]] | ||
| - | [[Category: Petersen, J]] | ||
| - | [[Category: Wissler, L]] | ||
| - | [[Category: Evenas, J]] | ||
| - | [[Category: Narjes, F]] | ||
[[Category: Svensson, K]] | [[Category: Svensson, K]] | ||
| - | [[Category: Feierberg, I]] | ||
| - | [[Category: Rohman, M]] | ||
| - | [[Category: Lepisto, M]] | ||
[[Category: Ward, A]] | [[Category: Ward, A]] | ||
| + | [[Category: Wissler, L]] | ||
| + | [[Category: Zhou, X]] | ||
| + | [[Category: Focused screening]] | ||
| + | [[Category: Hit validation]] | ||
| + | [[Category: Indole]] | ||
| + | [[Category: Pgds inhibitor]] | ||
| + | [[Category: Prostaglandin d2 synthase]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 12:36, 3 June 2015
Complex of human hematopoietic prostagandin D2 synthase (hH-PGDS) in complex with an active site inhibitor.
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Categories: Edfeldt, F | Evenas, J | Feierberg, I | Hansson, T | Lepisto, M | Narjes, F | Perry, M | Petersen, J | Rohman, M | Sivars, U | Svensson, K | Ward, A | Wissler, L | Zhou, X | Focused screening | Hit validation | Indole | Pgds inhibitor | Prostaglandin d2 synthase | Transferase
