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Structure of Cytochrome P450s and Personalized Drug

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Abstract:

Cytochrome P450s are the most important enzymes responsible for phase I drug metabolism. The polymorphic nature of cytochrome P450s largely influences individual drug responses, drug-drug interactions and induces adverse drug reactions. By far, thirty crystal structures of eight mammalian cytochrome P450s (CYP 2C5, 2C8, 2C9, 3A4, 2D6, 2B4, 2A6 and 1A2) have been published. This review focuses on the recent studies on the structures of cytochrome P450s: some characteristic features of these enzymes and many essential, conserved amino acids in the active sites have been identified. These results are of fundamental importance for drug development and understanding the metabolism for both endogenous and xenobiotic substrates. With the help of computational methods, the structural information will provide insights into personalization of drug treatments in both proper drug therapy and appropriate dosage of a certain drug.

Keywords: Cytochrome P450; crystal structure; personalized drug; polymorphism; structure-activity relationship

Document Type: Research Article

DOI: https://doi.org/10.2174/092986709787002727

Affiliations: Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, California 92130, USA.

Publication date: 2009-01-01

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