Abstract
1. Molecular modelling studies of CYP2B isoforms from rat (CYP2B1), rabbit (CYP2B4) and man (CYP2B6) are reported, with particular emphasis on substrate interactions with the human CYP2B isoform, CYP2B6. 2. The findings represent an advance on our previous study that focused primarily on the rat CYP2B isoform, CYP2B1, and involved homology modelling with substrate-free CYP102. 3. The current work utilizes the recently published substrate-bound CYP102 crystal structure as a template for construction of the CYP2B subfamily isoforms and shows, in particular, that known CYP2B6 substrate specificity and regioselectivity can be rationalized by putative active site interactions.
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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Animals
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Aryl Hydrocarbon Hydroxylases*
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Bacterial Proteins*
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Binding Sites
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Crystallography, X-Ray*
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Cytochrome P-450 CYP2B1 / chemistry*
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Cytochrome P-450 CYP2B6
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Cytochrome P-450 Enzyme System / chemistry*
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Humans
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Hydrogen-Ion Concentration
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Kinetics
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L-Lactate Dehydrogenase (Cytochrome)
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L-Lactate Dehydrogenase / chemistry*
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Mixed Function Oxygenases / chemistry*
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Models, Molecular*
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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NADPH-Ferrihemoprotein Reductase
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Oxidoreductases, N-Demethylating / chemistry*
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Rabbits
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Rats
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Sequence Homology, Amino Acid
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Steroid Hydroxylases / chemistry*
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Structure-Activity Relationship
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Substrate Specificity
Substances
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Bacterial Proteins
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Cytochrome P-450 Enzyme System
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Mixed Function Oxygenases
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L-Lactate Dehydrogenase
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L-Lactate Dehydrogenase (Cytochrome)
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Steroid Hydroxylases
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Aryl Hydrocarbon Hydroxylases
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CYP2B6 protein, human
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Cytochrome P-450 CYP2B1
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Cytochrome P-450 CYP2B6
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steroid 15-alpha-hydroxylase
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Oxidoreductases, N-Demethylating
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NADPH-Ferrihemoprotein Reductase
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flavocytochrome P450 BM3 monoxygenases