title: Human P450s involved in drug metabolism and the use of structural modelling for understanding substrate selectivity and binding affinity.
abstract: 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.
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK. d.lewis@surrey.ac.uk
authors.forename: D F V
authors.initials: DF
authors.lastname: Lewis
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
mesh_terms: 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
chemical_list: D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System