Abstract
Over the past decade, site-directed mutagenesis has become an essential tool in the study of mammalian cytochrome P450 structure-function relationships. Residues affecting substrate specificity, cooperativity, membrane localization, and interactions with redox partners have been identified using a combination of amino-acid sequence alignments, homology modeling, chimeragenesis, and site-directed mutagenesis. As homology modeling and substrate docking technology continue to improve, the ability to predict more precise functions for specific residues will also advance, making it possible to utilize site-directed mutagenesis to test these predictions. Future studies will employ site-directed mutagenesis to learn more about cytochrome P450 substrate access channels, to define the role of residues that do not lie within substrate recognition sites, to engineer additional soluble forms of microsomal cytochromes P450 for x-ray crystallography, and to engineer more efficient enzymes for drug activation and / or bioremediation.
Keywords: Mammalian Cytochrome P450 Structure, Mutagenesis, Chimeragenesis, Aflatoxin B1, naphthoflavone, Dehydroepiandrosterone
Current Drug Metabolism
Title: Analysis of Mammalian Cytochrome P450 Structure and Function by Site-Directed Mutagenesis
Volume: 2 Issue: 2
Author(s): T. L. Domanski and J. R. Halpert
Affiliation:
Keywords: Mammalian Cytochrome P450 Structure, Mutagenesis, Chimeragenesis, Aflatoxin B1, naphthoflavone, Dehydroepiandrosterone
Abstract: Over the past decade, site-directed mutagenesis has become an essential tool in the study of mammalian cytochrome P450 structure-function relationships. Residues affecting substrate specificity, cooperativity, membrane localization, and interactions with redox partners have been identified using a combination of amino-acid sequence alignments, homology modeling, chimeragenesis, and site-directed mutagenesis. As homology modeling and substrate docking technology continue to improve, the ability to predict more precise functions for specific residues will also advance, making it possible to utilize site-directed mutagenesis to test these predictions. Future studies will employ site-directed mutagenesis to learn more about cytochrome P450 substrate access channels, to define the role of residues that do not lie within substrate recognition sites, to engineer additional soluble forms of microsomal cytochromes P450 for x-ray crystallography, and to engineer more efficient enzymes for drug activation and / or bioremediation.
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Cite this article as:
Domanski L. T. and Halpert R. J., Analysis of Mammalian Cytochrome P450 Structure and Function by Site-Directed Mutagenesis, Current Drug Metabolism 2001; 2 (2) . https://dx.doi.org/10.2174/1389200013338612
DOI https://dx.doi.org/10.2174/1389200013338612 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
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