1W0E

Crystal structure of human cytochrome P450 3A4

1W0E の概要

• エントリーDOI: 10.2210/pdb1w0e/pdb
• 関連するPDBエントリー: 1W0F 1W0G
• 分子名称: CYTOCHROME P450 3A4, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• 機能のキーワード: oxidoreductase, nifedipine oxidase, cytochrome p450, electron transport, monooxygenase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 56097.97

構造登録者

Williams, P.A.,Cosme, J.,Vinkovic, D.M.,Ward, A.,Angove, H.C.,Day, P.J.,Vonrhein, C.,Tickle, I.J.,Jhoti, H. (登録日: 2004-06-03, 公開日: 2004-07-22, 最終更新日: 2024-05-08)

主引用文献

Williams, P.A.,Cosme, J.,Vinkovic, D.M.,Ward, A.,Angove, H.C.,Day, P.J.,Vonrhein, C.,Tickle, I.J.,Jhoti, H.
Crystal Structures of Human Cytochrome P450 3A4 Bound to Metyrapone and Progesterone
Science, 305:683-, 2004

PubMed Abstract: Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds and xenobiotics, such as pollutants, environmental compounds, and drug molecules. The microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the oxidative metabolism of more than 90% of marketed drugs. Cytochrome P450 3A4 (CYP3A4) metabolizes more drug molecules than all other isoforms combined. Here we report three crystal structures of CYP3A4: unliganded, bound to the inhibitor metyrapone, and bound to the substrate progesterone. The structures revealed a surprisingly small active site, with little conformational change associated with the binding of either compound. An unexpected peripheral binding site is identified, located above a phenylalanine cluster, which may be involved in the initial recognition of substrates or allosteric effectors.

PubMed: 15256616
DOI: 10.1126/SCIENCE.1099736

実験手法

X-RAY DIFFRACTION (2.8 Å)