Photoaffinity Ligands in the Study of Cytochrome P450 Active Site Structure
While photoaffinity ligands have been widely used to probe the structures of many receptors and nucleic acid binding proteins, their effective use in the study of cytochrome P450 structure is less established. Nevertheless, significant advances in this field have been made since the technique was first applied to P450cam in 1979. In several cases, especially studies involving P450s of the 1A and 2B families, peptides covalently modified with photoaffinity ligands have been isolated and characterized. Some of these peptides were predicted by molecular modeling to line substrate binding regions of the enzymes. Other data obtained from such studies were more difficult to reconcile with theory. This review addresses the status of photoaffinity labeling as a tool for studying cytochrome P450 structure. In addition, potential future directions in this field are discussed, including the development of heme-directed agents and validation of their effectiveness as photoaffinity ligands using sperm whale myoglobin as a test protein. The potential for hydroxyaromatic compounds to serve as photoactivated probes of active site nucleophiles is also discussed. This class of compounds and its derivatives has long been known in the fields of photochemistry and photophysics to be precursors of reactive radicals and quinone methides that are likely to serve as effective active site probes of the P450s.
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Document Type: Review Article
Publication date: 01 April 2003
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