6ztc: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6ztc]] is a 2 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=6ZTC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZTC FirstGlance]. <br>
<table><tr><td colspan='2'>[[6ztc]] is a 2 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=6ZTC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZTC FirstGlance]. <br>
</td></tr><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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QPN:1-[1-(3-fluorophenyl)-6,7-dihydro-4~{H}-pyrazolo[4,3-c]pyridin-5-yl]propan-1-one'>QPN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.84&#8491;</td></tr>
<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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QPN:1-[1-(3-fluorophenyl)-6,7-dihydro-4~{H}-pyrazolo[4,3-c]pyridin-5-yl]propan-1-one'>QPN</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=6ztc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ztc OCA], [https://pdbe.org/6ztc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ztc RCSB], [https://www.ebi.ac.uk/pdbsum/6ztc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ztc ProSAT]</span></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=6ztc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ztc OCA], [https://pdbe.org/6ztc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ztc RCSB], [https://www.ebi.ac.uk/pdbsum/6ztc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ztc ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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>  
[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 ==
Through an internal virtual screen at GlaxoSmithKline a distinct class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors were discovered. Careful evaluation of crystal structures and SAR led to a novel, potent, and orally active imidazopyridine inhibitor of H-PGDS, 20b. Herein, describes the identification of 2 classes of inhibitors, their syntheses, and their challenges.


A knowledge-based, structural-aided discovery of a novel class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors.,Deaton DN, Diaz E, Do Y, Gampe RT, Guss JH, Hancock AP, Hobbs H, Hodgson ST, Holt J, Jeune MR, Kahler KM, Kramer HF, Le J, Mortenson PN, Musetti C, Nolte RT, Orband-Miller LA, Peckham GE, Petrov KG, Pietrak BL, Poole C, Price DJ, Saxty G, Schulte CA, Shillings A, Smalley TL Jr, Somers DO, Stewart EL, Stuart JD, Thomson SA Bioorg Med Chem Lett. 2021 May 12:128113. doi: 10.1016/j.bmcl.2021.128113. PMID:33991628<ref>PMID:33991628</ref>
==See Also==
 
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ztc" style="background-color:#fffaf0;"></div>
== References ==
== References ==
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<references/>
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