Cytochrome P450 Substrate Specificities, Substrate Structural Templates and Enzyme Active Site Geometries
- 1 March 1999
- journal article
- review article
- Published by Walter de Gruyter GmbH in Drug Metabolism and Drug Interactions
- Vol. 15 (1) , 1-50
- https://doi.org/10.1515/dmdi.1999.15.1.1
Abstract
The structural characteristics of human cytochrome P450 substrates are outlined in the light of extensive studies on P450 substrate specificity. Templates of superimposed substrates for individual P450 isozymes are shown to fit the corresponding enzyme active sites, where contacts with specific amino acid residues appear to be involved in the interaction with each structural template. Procedures leading to the evaluation of likely P450 specificity, binding affinity and rate of metabolism are described in the context of key examples in which molecular modelling appears to rationalize experimentally observed findings.Keywords
This publication has 16 references indexed in Scilit:
- Molecular modelling of human CYP2C subfamily enzymes CYP2C9 and CYP2C19: rationalization of substrate specificity and site-directed mutagenesis experiments in the CYP2C subfamilyXenobiotica, 1998
- Prediction of Distribution Coefficient from Structure. 1. Estimation MethodJournal of Pharmaceutical Sciences, 1997
- Use of In Vitro and In Vivo Data to Estimate the Likelihood of Metabolic Pharmacokinetic InteractionsClinical Pharmacokinetics, 1997
- Prediction of Hepatic Clearance from Microsomes, Hepatocytes, and Liver SlicesDrug Metabolism Reviews, 1997
- Comparative MO-QSAR studies in various species including manChemico-Biological Interactions, 1996
- Designing safer chemicals: predicting the rates of metabolism of halogenated alkanes.Proceedings of the National Academy of Sciences, 1995
- Biochemistry and molecular biology of the human CYP2C subfamilyPharmacogenetics, 1994
- Reconciling the Magnitude of the Microscopic and Macroscopic Hydrophobic EffectsScience, 1991
- Species Differences in Metabolism and Pharmacokinetics: Are We Close to an Understanding?Drug Metabolism Reviews, 1991
- Haem exposure as the determinate of oxidation–reduction potential of haem proteinsNature, 1978