View source for 5ais


==Complex of human hematopoietic prostagandin D2 synthase (hH-PGDS) in complex with an active site inhibitor.==
<StructureSection load='5ais' size='340' side='right'caption='[[5ais]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ais]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AIS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AIS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CWC:4-(DIMETHYLAMINO)-N-[5-(1H-INDOL-4-YL)PYRIDIN-3-YL]BUTANAMIDE'>CWC</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=5ais FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ais OCA], [https://pdbe.org/5ais PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ais RCSB], [https://www.ebi.ac.uk/pdbsum/5ais PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ais ProSAT]</span></td></tr>
</table>
== Function ==
[https://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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ais" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Edfeldt F]]
[[Category: Evenas J]]
[[Category: Feierberg I]]
[[Category: Hansson T]]
[[Category: Lepisto M]]
[[Category: Narjes F]]
[[Category: Perry M]]
[[Category: Petersen J]]
[[Category: Rohman M]]
[[Category: Sivars U]]
[[Category: Svensson K]]
[[Category: Ward A]]
[[Category: Wissler L]]
[[Category: Zhou X]]