Structural models for cytochrome P450-mediated catalysis.
This review focuses on the structural models for cytochrome P450 that are improving our knowledge and understanding of the P450 catalytic cycle, and the way in which substrates bind to the enzyme leading to catalytic conversion and subsequent formation of mono-oxygenated metabolites. Various stages in the P450 reaction cycle have now been investigated using X-ray crystallography and electronic structure calculations, whereas homology modelling of mammalian P450s is currently revealing important aspects of pharmaceutical and other xenobiotic metabolism mediated by P450 involvement. These features are explored in the current review on P450-based catalysis, which emphasises the importance of structural modelling to our understanding of this enzyme's function. In addition, the results of various QSAR analyses on series of chemicals, which are metabolised via P450 enzymes, are presented such that the importance of electronic and other structural factors in explaining variations in rates of metabolism can be appreciated.
Lewis
David F V
DF
School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, UK. d.lewis@surrey.ac.uk
D000818:Animals; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D006801:Humans; D008956:Models, Chemical; D008961:Models, Structural
D003577:Cytochrome P-450 Enzyme System