Human P450s involved in drug metabolism and the use of structural modelling for understanding substrate selectivity and binding affinity

Xenobiotica. 2009 Aug;39(8):625-35. doi: 10.1080/00498250903000255.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Catalytic Domain
  • Crystallography, X-Ray
  • Cytochrome P-450 Enzyme System / chemistry*
  • Cytochrome P-450 Enzyme System / metabolism
  • Humans
  • Models, Molecular*
  • Pharmaceutical Preparations / chemistry*
  • Protein Binding
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Pharmaceutical Preparations
  • Cytochrome P-450 Enzyme System