1R9O

Crystal Structure of P4502C9 with Flurbiprofen bound

1R9O の概要

• エントリーDOI: 10.2210/pdb1r9o/pdb
• 関連するPDBエントリー: 1N6B 1NR6 1OG5 1PO5 1PQ2
• 分子名称: Cytochrome P450 2C9, PROTOPORPHYRIN IX CONTAINING FE, FLURBIPROFEN, ... (5 entities in total)
• 機能のキーワード: p450, monooxygenase, drug metabolizing enzyme, oxidoreductase, heme
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane; Peripheral membrane protein: P11712
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 55275.73

構造登録者

Wester, M.R.,Yano, J.K.,Schoch, G.A.,Griffin, K.J.,Stout, C.D.,Johnson, E.F. (登録日: 2003-10-30, 公開日: 2004-06-15, 最終更新日: 2023-08-23)

主引用文献

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

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: 15181000
DOI: 10.1074/jbc.M405427200

実験手法

X-RAY DIFFRACTION (2 Å)