5k0i
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==mpges1 bound to an inhibitor== | |
| + | <StructureSection load='5k0i' size='340' side='right' caption='[[5k0i]], [[Resolution|resolution]] 1.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5k0i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K0I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K0I FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6PW:1,5-ANHYDRO-2,3,4-TRIDEOXY-3-{[(4S)-3,3-DIMETHYL-1-(8-METHYLQUINOLIN-2-YL)PIPERIDINE-4-CARBONYL]AMINO}-D-ERYTHRO-HEXITOL'>6PW</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Prostaglandin-E_synthase Prostaglandin-E synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.99.3 5.3.99.3] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5k0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k0i OCA], [http://pdbe.org/5k0i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k0i RCSB], [http://www.ebi.ac.uk/pdbsum/5k0i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k0i ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PTGES_HUMAN PTGES_HUMAN]] Catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2).<ref>PMID:18682561</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Here we report on novel, potent 3,3-dimethyl substituted N-aryl piperidine inhibitors of microsomal prostaglandin E synthases-1(mPGES-1). Example 14 potently inhibited PGE2 synthesis in an ex vivo human whole blood (HWB) assay with an IC50 of 7nM. In addition, 14 had no activity in human COX-1 or COX-2 assays at 30muM, and failed to inhibit human mPGES-2 at 62.5muM in a microsomal prep assay. These data are consistent with selective mPGES-1-mediated reduction of PGE2. In dog, 14 had oral bioavailability (74%), clearance (3.62mL/(min*kg)) and volume of distribution (Vd,ss=1.6L/kg) values within our target ranges. For these reasons, 14 was selected for further study. | ||
| - | + | Characterization of 3,3-dimethyl substituted N-aryl piperidines as potent microsomal prostaglandin E synthase-1 inhibitors.,Kuklish SL, Antonysamy S, Bhattachar SN, Chandrasekhar S, Fisher MJ, Fretland AJ, Gooding K, Harvey A, Hughes NE, Luz JG, Manninen PR, McGee JE, Navarro A, Norman BH, Partridge KM, Quimby SJ, Schiffler MA, Sloan AV, Warshawsky AM, York JS, Yu XP Bioorg Med Chem Lett. 2016 Oct 1;26(19):4824-8. doi: 10.1016/j.bmcl.2016.08.023. , Epub 2016 Aug 10. PMID:27554445<ref>PMID:27554445</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Luz, J | + | <div class="pdbe-citations 5k0i" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Prostaglandin-E synthase]] | ||
| + | [[Category: Kuklish, S L]] | ||
| + | [[Category: Luz, J G]] | ||
| + | [[Category: Inflammation]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Isomerase-isomerase inhibitor complex]] | ||
| + | [[Category: Mpges1]] | ||
| + | [[Category: Pain]] | ||
Revision as of 15:12, 14 September 2016
mpges1 bound to an inhibitor
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