Review
Structural diversity of human xenobiotic-metabolizing cytochrome P450 monooxygenases

https://doi.org/10.1016/j.bbrc.2005.08.190Get rights and content

Abstract

Cytochrome P450 monooxygenases provide important pathways for the metabolic clearance of drugs and toxins in humans. These enzymes are expressed from multiple genes and exhibit complex patterns of differential and overlapping substrate selectivity. Recent structures of microsomal P450s determined by X-ray crystallography have provided a structural basis for understanding differences in substrate recognition. This review will describe similarities and differences in the active site structures of four human microsomal cytochrome P450 monooxygenases, 2A6, 2C8, 2C9, and 3A4, that contribute extensively to drug and toxin metabolism.

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Acknowledgments

The authors’ studies of human drug-metabolizing P450s are supported by NIH Grant GM031001 and by Pfizer Global Research and Development.

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    Abbreviations: CYP, cytochrome P450; PDB, Protein Data Bank (http://www.rcsb.org/pdb/).

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