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 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.
Lewis
D F V
DF
Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK. d.lewis@surrey.ac.uk
Ito
Y
Y
D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System