title: Comparisons of catalytic selectivity of cytochrome P450 subfamily enzymes from different species.
abstract: Historically there has been considerable interest in comparing patterns of biotransformation of xenobiotic chemicals in experimental animal models and humans, e.g. in areas such as drug metabolism and chemical carcinogenesis. With the availability of more basic knowledge it has become possible to attribute the oxidation of selected chemicals to individual cytochrome P450 (P450) enzymes in animals and humans. Further, these P450s can be characterized by their classification into distinct subfamilies, which are defined as having > 59% amino acid sequence identity. Questions arise about how similar these enzymes are with regard to structure and function. More practically, how much can be predicted about reaction specificity and catalysis? In order to address these issues, we need to consider not only the relatedness of P450s from different species but also (i) functional similarity within P450 subfamilies and (ii) the effects of small changes imposed by site-directed mutagenesis. Relationships in the P450 1A, 2A, 2B, 2C, 2D, 2E, 3A, and 17A subfamilies are briefly reviewed. Overall functional similarity is generally seen in subfamily enzymes but many examples exist of important changes in catalysis due to very small differences, even a single conservative amino acid substitution. Some general conclusions are presented about predictability within various P450 subfamilies.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA. guengerich@toxicology.mc.vanderbilt.edu
authors.forename: F P
authors.initials: FP
authors.lastname: Guengerich
mesh_terms: D000483:Alleles; D000818:Animals; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D011110:Polymorphism, Genetic; D013045:Species Specificity
chemical_list: D003577:Cytochrome P-450 Enzyme System