4YK5
Crystal Structures of mPGES-1 Inhibitor Complexes
Summary for 4YK5
| Entry DOI | 10.2210/pdb4yk5/pdb |
| Descriptor | Prostaglandin E synthase, 3-[1-(4-chlorobenzyl)-5-(2-fluoro-2'-methylbiphenyl-4-yl)-3-methyl-1H-indol-2-yl]-2,2-dimethylpropanoic acid, 2-(2-METHOXYETHOXY)ETHANOL, ... (8 entities in total) |
| Functional Keywords | inflammation, isomerase-isomerase inhibitor complex, isomerase/isomerase inhibitor |
| Biological source | Homo sapiens (Human) |
| Cellular location | Membrane ; Multi-pass membrane protein : O14684 |
| Total number of polymer chains | 1 |
| Total formula weight | 18967.86 |
| Authors | Luz, J.G.,Antonysamy, S.,Kuklish, S.L.,Fisher, M.J. (deposition date: 2015-03-04, release date: 2015-07-15, Last modification date: 2024-02-28) |
| Primary citation | Luz, J.G.,Antonysamy, S.,Kuklish, S.L.,Condon, B.,Lee, M.R.,Allison, D.,Yu, X.P.,Chandrasekhar, S.,Backer, R.,Zhang, A.,Russell, M.,Chang, S.S.,Harvey, A.,Sloan, A.V.,Fisher, M.J. Crystal Structures of mPGES-1 Inhibitor Complexes Form a Basis for the Rational Design of Potent Analgesic and Anti-Inflammatory Therapeutics. J.Med.Chem., 58:4727-4737, 2015 Cited by PubMed Abstract: Microsomal prostaglandin E synthase 1 (mPGES-1) is an α-helical homotrimeric integral membrane inducible enzyme that catalyzes the formation of prostaglandin E2 (PGE2) from prostaglandin H2 (PGH2). Inhibition of mPGES-1 has been proposed as a therapeutic strategy for the treatment of pain, inflammation, and some cancers. Interest in mPGES-1 inhibition can, in part, be attributed to the potential circumvention of cardiovascular risks associated with anti-inflammatory cyclooxygenase 2 inhibitors (coxibs) by targeting the prostaglandin pathway downstream of PGH2 synthesis and avoiding suppression of antithrombotic prostacyclin production. We determined the crystal structure of mPGES-1 bound to four potent inhibitors in order to understand their structure-activity relationships and provide a framework for the rational design of improved molecules. In addition, we developed a light-scattering-based thermal stability assay to identify molecules for crystallographic studies. PubMed: 25961169DOI: 10.1021/acs.jmedchem.5b00330 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.42 Å) |
Structure validation
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