3PDC
Crystal structure of hydrolase domain of human soluble epoxide hydrolase complexed with a benzoxazole inhibitor
Summary for 3PDC
| Entry DOI | 10.2210/pdb3pdc/pdb |
| Related | 1S8O 1VJ5 1ZD2 3i28 3iIy |
| Descriptor | Epoxide hydrolase 2, N-(5-chloro-1,3-benzoxazol-2-yl)-2-cyclopentylacetamide (3 entities in total) |
| Functional Keywords | epoxide hydrolase, hydrolase, hypertension, beta barrel, alpha/beta hydrolase fold; epoxide hydrolase fold, acts on epoxides (alkene oxides, oxiranes) and arene oxides. plays a role in xenobiotic metabolism by degrading potentially toxic epoxides. also determines steady-state levels of physiological mediators. has low phosphatase activity, binds mg2+, acetylation of lysine, cytoplasm; peroxisome, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: P34913 |
| Total number of polymer chains | 2 |
| Total formula weight | 79181.50 |
| Authors | Kurumbail, R.G.,Williams, J.M. (deposition date: 2010-10-22, release date: 2011-04-06, Last modification date: 2023-09-06) |
| Primary citation | Xing, L.,McDonald, J.J.,Kolodziej, S.A.,Kurumbail, R.G.,Williams, J.M.,Warren, C.J.,O'Neal, J.M.,Skepner, J.E.,Roberds, S.L. Discovery of potent inhibitors of soluble epoxide hydrolase by combinatorial library design and structure-based virtual screening. J.Med.Chem., 54:1211-1222, 2011 Cited by PubMed Abstract: Structure-based virtual screening was applied to design combinatorial libraries to discover novel and potent soluble epoxide hydrolase (sEH) inhibitors. X-ray crystal structures revealed unique interactions for a benzoxazole template in addition to the conserved hydrogen bonds with the catalytic machinery of sEH. By exploitation of the favorable binding elements, two iterations of library design based on amide coupling were employed, guided principally by the docking results of the enumerated virtual products. Biological screening of the libraries demonstrated as high as 90% hit rate, of which over two dozen compounds were single digit nanomolar sEH inhibitors by IC(50) determination. In total the library design and synthesis produced more than 300 submicromolar sEH inhibitors. In cellular systems consistent activities were demonstrated with biochemical measurements. The SAR understanding of the benzoxazole template provides valuable insights into discovery of novel sEH inhibitors as therapeutic agents. PubMed: 21302953DOI: 10.1021/jm101382t PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
Download full validation report
