4I8V

Human Cytochrome P450 1A1 in complex with alpha-naphthoflavone

4I8V の概要

• エントリーDOI: 10.2210/pdb4i8v/pdb
• 分子名称: Cytochrome P450 1A1, PROTOPORPHYRIN IX CONTAINING FE, 2-PHENYL-4H-BENZO[H]CHROMEN-4-ONE, ... (5 entities in total)
• 機能のキーワード: monooxygenase, cytochrome p450, p450, cyp1a1, p450 1a1, heme, oxidoreductase, aryl hydrocarbon hydroxylase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane; Peripheral membrane protein: P04798
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 227517.78

構造登録者

Walsh, A.A.,Scott, E.E. (登録日: 2012-12-04, 公開日: 2013-02-27, 最終更新日: 2023-09-20)

主引用文献

Walsh, A.A.,Szklarz, G.D.,Scott, E.E.
Human Cytochrome P450 1A1 Structure and Utility in Understanding Drug and Xenobiotic Metabolism.
J.Biol.Chem., 288:12932-12943, 2013

PubMed Abstract: Cytochrome P450 (CYP) 1A1 is an extrahepatic monooxygenase involved in the metabolism of endogenous substrates and drugs, as well as the activation of certain toxins and environmental pollutants. CYP1A1 is particularly well known for its ability to biotransform polycyclic aromatic hydrocarbons, such as benzo[a]pyrene in tobacco smoke, into carcinogens. CYP1A1 possesses functional similarities and differences with human CYP1A2 and CYP1B1 enzymes, but the structural basis for this has been unclear. We determined a 2.6 Å structure of human CYP1A1 with the inhibitor α-naphthoflavone. α-Naphthoflavone binds within an enclosed active site, with the planar benzochromen-4-one core packed flat against the I helix that composes one wall of the active site, and the 2-phenyl substituent oriented toward the catalytic heme iron. Comparisons with previously determined structures of the related cytochrome P450 1A2 and 1B1 enzymes reveal distinct features among the active sites that may underlie the functional variability of these enzymes. Finally, docking studies probed the ability of CYP1A structures to assist in understanding their known in vitro interactions with several typical substrates and inhibitors.

PubMed: 23508959
DOI: 10.1074/jbc.M113.452953

実験手法

X-RAY DIFFRACTION (2.6 Å)