Human P450s involved in drug metabolism and the use of structural modelling for understanding substrate selectivity and binding affinity

The human cytochrome P450 enzymes and their substrates are reviewed, together with current knowledge on the three-dimensional structures of P450s obtained from X-ray crystallographic studies and from homology modelling based on mammalian P450 template crystal structures. There is a particular focus...

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Bibliographic Details
Published in:Xenobiotica 2009-08, Vol.39 (8), p.625-635
Main Authors: Lewis, D. F. V., Ito, Y.
Format: Article
Language:English
Subjects:
binding affinity
Catalytic Domain
Crystallography, X-Ray
Cytochrome P-450 Enzyme System - chemistry
Cytochrome P-450 Enzyme System - metabolism
Human cytochrome P450s
Humans
Models, Molecular
Pharmaceutical Preparations - chemistry
Protein Binding
Structure-Activity Relationship
substrate selectivity
Substrate Specificity
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Summary:The human cytochrome P450 enzymes and their substrates are reviewed, together with current knowledge on the three-dimensional structures of P450s obtained from X-ray crystallographic studies and from homology modelling based on mammalian P450 template crystal structures. There is a particular focus on human Phase 1 drug metabolism mediated by P450s, and a rationalization of their substrate selectivities and binding strengths in terms of lipophilicity and active site interactions. The combination of molecular modelling and quantitative structure-activity relationship (QSAR) studies facilitates understanding of the factors which determine substrate selectivity and binding to the human drug-metabolizing P450s.
ISSN:0049-8254
1366-5928
DOI:10.1080/00498250903000255