P450 structures and oxidative metabolism of xenobiotics.
This review focuses on the structural models for cytochrome P450, which 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 modeling 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 emphasizes the importance of structural modeling to our understanding of this enzyme's function. In addition, the results of various quantitative structure-activity relationships (QSAR) analyses on series of chemicals, which are metabolized 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. As an important example of biocatalysis, the P450 system has a major future as an enzyme for use in many biotechnological applications, including biodegradation and bioremediation.
Lewis
David F V
DF
School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK. d.lewis@surrey.ac.uk
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D015262:Xenobiotics / Q000378:metabolism*
D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System