Analysis of the catalytic specificity of cytochrome P450 enzymes through site-directed mutagenesis.
The way in which structural diversity encodes the capacity of individual P450 enzymes to metabolize multiple, structurally distinct substrates remains largely unknown. The tools of molecular biology provide a means of identifying amino acid residues among closely related P450s that are determinants of their distinct catalytic properties. Work in our laboratory has identified two substrate specificity-determining segments of the amino acid sequences of subfamily 2C P450s. A pattern has emerged from this work, and that of others, which suggests a model for the structural basis of P450 catalytic diversity.
Johnson
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Scripps Research Institute, Division of Biochemistry, La Jolla, California 92037.
Kronbach
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Hsu
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D000595:Amino Acid Sequence; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D014644:Genetic Variation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D012326:RNA Splicing; D012689:Sequence Homology, Nucleic Acid; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000378:metabolism
D003577:Cytochrome P-450 Enzyme System; D013255:Steroid 21-Hydroxylase