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

Expert Opinion on Drug Metabolism & Toxicology
David F V Lewis, Yuko Ito

Abstract

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 K(m) values obtained from enzyme kinetics.

References

May 9, 2002·Drug Metabolism Reviews·Slobodan Rendic
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Jun 18, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·R Scott Obach, Anne E Reed-Hagen
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Citations

Oct 21, 2009·Genes & Nutrition·Arjan ScheepensJames W Paxton
Dec 16, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jyothi C TalakadDeepak Dalvie
May 3, 2011·Archives of Toxicology·Sarah AdlerJosé-Manuel Zaldivar
Jan 8, 2013·Expert Opinion on Drug Metabolism & Toxicology·Yan Li, James W Paxton
Jul 16, 2009·Drug Metabolism Reviews·Alan BoobisKeith Tipton
Apr 21, 2010·Expert Opinion on Drug Metabolism & Toxicology·David F V Lewis, Yuko Ito
Oct 16, 2010·Bioinformatics·Patrik RydbergLars Olsen
Mar 18, 2015·Bioinformatics·Anastasia RudikVladimir Poroikov
May 1, 2009·Bioanalysis·Olavi PelkonenHannu Raunio
Sep 18, 2016·Advanced Drug Delivery Reviews·Yan LiJames W Paxton
Jun 12, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·D F V Lewis, Y Ito
Nov 8, 2017·Current Medicinal Chemistry·Agostino BrunoMarco Radi
Jun 12, 2020·Journal of Chemical Information and Modeling·Noah R FlynnS Joshua Swamidass
Jan 15, 2014·Journal of Chemical Information and Modeling·Anastasia V RudikVladimir V Poroikov

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