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.
Acknowledgements
This original paper is dedicated to the memory of Professor Gordon Gibson, a friend and colleague of many years standing, who is sadly no longer with us to encourage and inspire others by the force of his character and intellect. The financial support of ExxonMobil Biomedical Sciences, Inc., The British Technology Group, and the Friends of the University of Surrey is gratefully acknowledged by DFVL. Yuko Ito would like to thank the Japanese Foundation for sponsoring a visiting scientist PhD studentship at the University of Surrey.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.