Progress in cytochrome P450 active site modeling

Carol A. Kemp, Jean Didier Maréchal, Michael J. Sutcliffe

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)


Models capable of predicting the possible involvement of cytochromes P450 in the metabolism of drugs or drug candidates are important tools in drug discovery and development. Ideally, functional information would be obtained from crystal structures of all the cytochromes P450 of interest. Initially, only crystal structures of distantly related bacterial cytochromes P450 were available-comparative modeling techniques were used to bridge the gap and produce structural models of human cytochromes P450, and thereby obtain some useful functional information. A significant step forward in the reliability of these models came four years ago with the first crystal structure of a mammalian cytochrome P450, rabbit CYP2C5, followed by the structures of two human enzymes, CYP2C8 and CYP2C9, and a second rabbit enzyme, CYP2B4. The evolution of a CYP2D6 model, leading to the validation of the model as an in silico tool for predicting binding and metabolism, is presented as a case study.

Original languageEnglish
Pages (from-to)361-368
Number of pages8
JournalArchives of biochemistry and biophysics
Issue number2
Publication statusPublished - 15 Jan 2005


  • Cytochromes P450
  • Drug binding
  • Drug discovery
  • Drug metabolism
  • Predictive tools
  • Structural models


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