2vd1

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[[Image:2vd1.jpg|left|200px]]
 
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==Complex structure of prostaglandin D2 synthase at 2.25A.==
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The line below this paragraph, containing "STRUCTURE_2vd1", creates the "Structure Box" on the page.
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<StructureSection load='2vd1' size='340' side='right'caption='[[2vd1]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2vd1]] 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=2VD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VD1 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D28:4-{[4-(4-FLUORO-3-METHYLPHENYL)-1,3-THIAZOL-2-YL]AMINO}-2-HYDROXYBENZOIC+ACID'>D28</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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{{STRUCTURE_2vd1| PDB=2vd1 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vd1 OCA], [https://pdbe.org/2vd1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vd1 RCSB], [https://www.ebi.ac.uk/pdbsum/2vd1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vd1 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vd/2vd1_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2vd1 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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'''COMPLEX STRUCTURE OF PROSTAGLANDIN D2 SYNTHASE AT 2.25A.'''
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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>
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==Overview==
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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.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2VD1 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VD1 OCA].
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</div>
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<div class="pdbe-citations 2vd1" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/18341273 18341273]
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*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Prostaglandin-D synthase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Dahmen J]]
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[[Category: Dahmen, J.]]
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[[Category: Edman K]]
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[[Category: Edman, K.]]
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[[Category: Folmer RHA]]
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[[Category: Folmer, R H.A.]]
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[[Category: Groth-Clausen I]]
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[[Category: Groth-Clausen, I.]]
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[[Category: Hawtin P]]
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[[Category: Hawtin, P.]]
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[[Category: Hohwy M]]
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[[Category: Hohwy, M.]]
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[[Category: Lundquist B]]
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[[Category: Lundquist, B.]]
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[[Category: Persdotter S]]
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[[Category: Persdotter, S.]]
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[[Category: Spadola L]]
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[[Category: Spadola, L.]]
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[[Category: Von Wachenfeldt K]]
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[[Category: Von, K.]]
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[[Category: Wachenfeldt]]
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[[Category: Asthma]]
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[[Category: Cytoplasm]]
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[[Category: Fatty acid biosynthesis]]
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[[Category: Isomerase]]
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[[Category: Lipid synthesis]]
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[[Category: Pgd]]
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[[Category: Prostaglandin biosynthesis]]
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[[Category: Prostaglandin d2 synthase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 16 23:07:35 2008''
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Current revision

Complex structure of prostaglandin D2 synthase at 2.25A.

PDB ID 2vd1

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