1R9O
Crystal Structure of P4502C9 with Flurbiprofen bound
Summary for 1R9O
| Entry DOI | 10.2210/pdb1r9o/pdb |
| Related | 1N6B 1NR6 1OG5 1PO5 1PQ2 |
| Descriptor | Cytochrome P450 2C9, PROTOPORPHYRIN IX CONTAINING FE, FLURBIPROFEN, ... (5 entities in total) |
| Functional Keywords | p450, monooxygenase, drug metabolizing enzyme, oxidoreductase, heme |
| Biological source | Homo sapiens (human) |
| Cellular location | Endoplasmic reticulum membrane; Peripheral membrane protein: P11712 |
| Total number of polymer chains | 1 |
| Total formula weight | 55275.73 |
| Authors | Wester, M.R.,Yano, J.K.,Schoch, G.A.,Griffin, K.J.,Stout, C.D.,Johnson, E.F. (deposition date: 2003-10-30, release date: 2004-06-15, Last modification date: 2023-08-23) |
| Primary citation | Wester, M.R.,Yano, J.K.,Schoch, G.A.,Yang, C.,Griffin, K.J.,Stout, C.D.,Johnson, E.F. The Structure of Human Cytochrome P450 2C9 Complexed with Flurbiprofen at 2.0 A Resolution J.Biol.Chem., 279:35630-35637, 2004 Cited by PubMed Abstract: The structure of human P450 2C9 complexed with flurbiprofen was determined to 2.0 A by x-ray crystallography. In contrast to other structurally characterized P450 2C enzymes, 2C5, 2C8, and a 2C9 chimera, the native catalytic domain of P450 2C9 differs significantly in the conformation of the helix F to helix G region and exhibits an extra turn at the N terminus of helix A. In addition, a distinct conformation of the helix B to helix C region allows Arg-108 to hydrogen bond with Asp-293 and Asn-289 on helix I and to interact directly with the carboxylate of flurbiprofen. These interactions position the substrate for regioselective oxidation in a relatively large active site cavity and are likely to account for the high catalytic efficiency exhibited by P450 2C9 for the regioselective oxidation of several anionic non-steroidal anti-inflammatory drugs. The structure provides a basis for interpretation of a number of observations regarding the substrate selectivity of P450 2C9 and the observed effects of mutations on catalysis. PubMed: 15181000DOI: 10.1074/jbc.M405427200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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