Abstract
1. The results of molecular modelling of human CYP2C isozymes, CYP2C9 and CYP2C19, are reported based on an alignment with a bacterial form of the enzyme, CYP102. 2. The three-dimensional structures of the CYP2C enzymes are consistent with known experimental evidence from site-directed mutagenesis, antibody recognition and regiospecificity of substrate metabolism. 3. The variations in substrate specificity between CYP2C9 and CYP2C19 can be rationalized in terms of single amino acid residue changes within the putative active site region, of which I99H appears to be the most significant.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Aryl Hydrocarbon Hydroxylases*
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Cytochrome P-450 CYP2C19
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Cytochrome P-450 CYP2C9
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Cytochrome P-450 Enzyme System / chemistry*
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Cytochrome P-450 Enzyme System / genetics*
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Cytochrome P-450 Enzyme System / metabolism
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Humans
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Isoenzymes / chemistry*
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Isoenzymes / genetics*
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Isoenzymes / metabolism
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Mixed Function Oxygenases / chemistry*
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Mixed Function Oxygenases / genetics*
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Mixed Function Oxygenases / metabolism
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Models, Molecular*
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Sequence Alignment
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Species Specificity
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Steroid 16-alpha-Hydroxylase*
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Steroid Hydroxylases / chemistry*
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Steroid Hydroxylases / genetics*
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Steroid Hydroxylases / metabolism
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Substrate Specificity
Substances
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Isoenzymes
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Cytochrome P-450 Enzyme System
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Mixed Function Oxygenases
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Steroid Hydroxylases
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CYP2C9 protein, human
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Cytochrome P-450 CYP2C9
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Aryl Hydrocarbon Hydroxylases
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CYP2C19 protein, human
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Cytochrome P-450 CYP2C19
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Steroid 16-alpha-Hydroxylase