Human cytochromes P450 in the metabolism of drugs: new molecular models of enzyme-substrate interactions

被引：26

作者：

Lewis, David F. V. ^{[1
]}

Ito, Yuko ^{[2
]}

机构：

[1] Univ Surrey, Ctr Toxicol, Fac Med & Hlth Sci, Surrey GU2 7XH, England

[2] Yokohama City Univ, Grad Sch Integrated Sci, Div Sci Biol Supramol Syst, Tsurumi Ku, Kanagawa 2300045, Japan

来源：

EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY | 2008年 / 4卷 / 09期

关键词：

cytochromes P450; drug metabolism; enzyme structures; molecular modelling;

D O I：

10.1517/17425255.4.9.1181

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The overall predictive ability of molecular modelling, as applied to the cytochrome P450 (CYP) system, is analysed in the light of current developments in a variety of techniques, including X-ray crystallography, molecular biology, enzyme kinetics, molecular mechanics and dynamics, in relation to its relevance to drug metabolism in humans. This review demonstrates that it is possible to generate realistic models for the major human CYPs, which metabolise xenobiotics that compare favourably with crystal structures, and thus may be used to derive substrate binding energies that agree closely with experimental Km values obtained from enzyme kinetics.

引用

页码：1181 / 1186

页数：6

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