2cvd

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{{Seed}}
 
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[[Image:2cvd.png|left|200px]]
 
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==Crystal structure analysis of human hematopoietic prostaglandin D synthase complexed with HQL-79==
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The line below this paragraph, containing "STRUCTURE_2cvd", creates the "Structure Box" on the page.
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<StructureSection load='2cvd' size='340' side='right'caption='[[2cvd]], [[Resolution|resolution]] 1.45&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'>[[2cvd]] 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=2CVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CVD 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]] 1.45&#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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=HQL:4-(BENZHYDRYLOXY)-1-[3-(1H-TETRAAZOL-5-YL)PROPYL]PIPERIDINE'>HQL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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{{STRUCTURE_2cvd| PDB=2cvd | 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=2cvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cvd OCA], [https://pdbe.org/2cvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cvd RCSB], [https://www.ebi.ac.uk/pdbsum/2cvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cvd 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/cv/2cvd_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=2cvd 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 determined the crystal structure of human hematopoietic prostaglandin (PG) D synthase (H-PGDS) as the quaternary complex with glutathione (GSH), Mg2+, and an inhibitor, HQL-79, having anti-inflammatory activities in vivo, at a 1.45-A resolution. In the quaternary complex, HQL-79 was found to reside within the catalytic cleft between Trp104 and GSH. HQL-79 was stabilized by interaction of a phenyl ring of its diphenyl group with Trp104 and by its piperidine group with GSH and Arg14 through water molecules, which form a network with hydrogen bonding and salt bridges linked to Mg2+. HQL-79 inhibited human H-PGDS competitively against the substrate PGH2 and non-competitively against GSH with Ki of 5 and 3 microm, respectively. Surface plasmon resonance analysis revealed that HQL-79 bound to H-PGDS with an affinity that was 12-fold higher in the presence of GSH and Mg2+ (Kd, 0.8 microm) than in their absence. Mutational studies revealed that Arg14 was important for the Mg2+-mediated increase in the binding affinity of H-PGDS for HQL-79, and that Trp104, Lys112, and Lys198 were important for maintaining the HQL-binding pocket. HQL-79 selectively inhibited PGD2 production by H-PGDS-expressing human megakaryocytes and rat mastocytoma cells with an IC50 value of about 100 microm but only marginally affected the production of other prostanoids, suggesting the tight functional engagement between H-PGDS and cyclooxygenase. Orally administered HQL-79 (30 mg/kg body weight) inhibited antigen-induced production of PGD2, without affecting the production of PGE2 and PGF2alpha, and ameliorated airway inflammation in wild-type and human H-PGDS-overexpressing mice. Knowledge about this structure of quaternary complex is useful for understanding the inhibitory mechanism of HQL-79 and should accelerate the structure-based development of novel anti-inflammatory drugs that inhibit PGD2 production specifically.
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===Crystal structure analysis of human hematopoietic prostaglandin D synthase complexed with HQL-79===
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Structural and functional characterization of HQL-79, an orally selective inhibitor of human hematopoietic prostaglandin D synthase.,Aritake K, Kado Y, Inoue T, Miyano M, Urade Y J Biol Chem. 2006 Jun 2;281(22):15277-86. Epub 2006 Mar 17. PMID:16547010<ref>PMID:16547010</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2cvd" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_16547010}}, adds the Publication Abstract to the page
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*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 16547010 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_16547010}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2CVD is a 4 chains structure of sequences 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=2CVD OCA].
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==Reference==
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<ref group="xtra">PMID:16547010</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Aritake, K.]]
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[[Category: Large Structures]]
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[[Category: Inoue, T.]]
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[[Category: Aritake K]]
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[[Category: Kado, Y.]]
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[[Category: Inoue T]]
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[[Category: Miyano, M.]]
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[[Category: Kado Y]]
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[[Category: Urade, Y.]]
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[[Category: Miyano M]]
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[[Category: Glutathione-s-transferase]]
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[[Category: Urade Y]]
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[[Category: Isomerase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 19:41:51 2009''
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Current revision

Crystal structure analysis of human hematopoietic prostaglandin D synthase complexed with HQL-79

PDB ID 2cvd

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