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Molecular modelling of CYP1 family enzymes CYP1A1, CYP1A2, CYP1A6 and CYP1B1 based on sequence homology with CYP102.

Lewis DF, Lake BG, George SG, Dickins M, Eddershaw PJ, Tarbit MH, Beresford AP, Goldfarb PS, Guengerich FP
Toxicology. 1999 139 (1-2): 53-79

PMID: 10614688 · DOI:10.1016/s0300-483x(99)00098-0

Molecular modelling of a number of CYP1 family enzymes from rat, plaice and human is described based on amino acid sequence homology with the haemoprotein domain of CYP102, a unique bacterial P450 of known structure. The interaction of various substrates and inhibitors within the putative active sites of rat CYP1A1, human CYP1A2, a fish CYP1 enzyme CYP1A6 (from plaice) and human CYP1B1, is shown to be consistent with P450-mediated oxidation in each example or, in the case of inhibitors, mechanism of inhibition. It is reported that relatively small changes between the enzymes' active site regions assist in the rationalization of CYP1 enzyme preferences for particular substrate types, and a template of superimposed CYP1A2 substrates is shown to fit the putative active site of the human CYP1A2 enzyme.

MeSH Terms (26)

Animals Aryl Hydrocarbon Hydroxylases Bacterial Proteins Cricetinae Cytochrome P-450 CYP1A1 Cytochrome P-450 CYP1A2 Cytochrome P-450 CYP1A2 Inhibitors Cytochrome P-450 CYP1B1 Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Enzyme System Enzyme Inhibitors Flatfishes Humans Hydrogen Bonding Mice Mixed Function Oxygenases Models, Molecular Mutagenesis, Site-Directed NADPH-Ferrihemoprotein Reductase Oxidation-Reduction Rabbits Rats Sequence Homology, Amino Acid Species Specificity Structure-Activity Relationship Xenobiotics

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