View source for 2vcq


==Complex structure of prostaglandin D2 synthase at 1.95A.==
<StructureSection load='2vcq' size='340' side='right'caption='[[2vcq]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2vcq]] 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=2VCQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VCQ 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]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D25:3-PHENYL-5-(1H-PYRAZOL-3-YL)ISOXAZOLE'>D25</scene>, <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'>[https://proteopedia.org/fgij/fg.htm?mol=2vcq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vcq OCA], [https://pdbe.org/2vcq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vcq RCSB], [https://www.ebi.ac.uk/pdbsum/2vcq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vcq 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> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vc/2vcq_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vcq ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We describe the discovery of novel inhibitors of prostaglandin D2 synthase (PGDS) through fragment-based lead generation and structure-based drug design. A library of 2500 low-molecular-weight compounds was screened using 2D nuclear magnetic resonance (NMR), leading to the identification of 24 primary hits. Structure determination of protein-ligand complexes with the hits enabled a hit optimization process, whereby we harvested increasingly more potent inhibitors out of our corporate compound collection. Two iterative cycles were carried out, comprising NMR screening, molecular modeling, X-ray crystallography, and in vitro biochemical testing. Six novel high-resolution PGDS complex structures were determined, and 300 hit analogues were tested. This rational drug design procedure culminated in the discovery of 24 compounds with an IC 50 below 1 microM in the in vitro assay. The best inhibitor (IC 50 = 21 nM) is one of the most potent inhibitors of PGDS to date. As such, it may enable new functional in vivo studies of PGDS and the prostaglandin metabolism pathway.

Novel prostaglandin d synthase inhibitors generated by fragment-based drug design.,Hohwy M, Spadola L, Lundquist B, Hawtin P, Dahmen J, Groth-Clausen I, Nilsson E, Persdotter S, von Wachenfeldt K, Folmer RH, Edman K J Med Chem. 2008 Apr 10;51(7):2178-86. Epub 2008 Mar 15. PMID:18341273<ref>PMID:18341273</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2vcq" 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: Dahmen J]]
[[Category: Edman K]]
[[Category: Folmer RHA]]
[[Category: Groth-Clausen I]]
[[Category: Hawtin P]]
[[Category: Hohwy M]]
[[Category: Lundquist B]]
[[Category: Persdotter S]]
[[Category: Spadola L]]
[[Category: Von Wachenfeldt K]]