Structural diversity of human xenobiotic-metabolizing cytochrome P450 monooxygenases.
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.
Johnson
Eric F
EF
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. johnson@scripps.edu
Stout
C David
CD
D000595:Amino Acid Sequence; D001189:Aryl Hydrocarbon Hydroxylases / Q000737:chemistry* / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D015262:Xenobiotics / Q000378:metabolism*
D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; C104464:CYP3A protein, human; D065637:Cytochrome P-450 CYP2A6; D065727:Cytochrome P-450 CYP2C8; D051544:Cytochrome P-450 CYP3A