title: Conformational plasticity and structure/function relationships in cytochromes P450.
abstract: The cytochrome P450s are a superfamily of enzymes that are found in all kingdoms of living organisms, and typically catalyze the oxidative addition of atomic oxygen to an unactivated C-C or C-H bond. Over 8000 nonredundant sequences of putative and confirmed P450 enzymes have been identified, but three-dimensional structures have been determined for only a small fraction of these. While all P450 enzymes for which structures have been determined share a common global fold, the flexibility and modularity of structure around the active site account for the ability of P450 enzymes to accommodate a vast number of structurally dissimilar substrates and support a wide range of selective oxidations. In this review, known P450 structures are compared, and some structural criteria for prediction of substrate selectivity and reaction type are suggested. The importance of dynamic processes such as redox-dependent and effector-induced conformational changes in determining catalytic competence and regio- and stereoselectivity is discussed, and noncrystallographic methods for characterizing P450 structures and dynamics, in particular, mass spectrometry and nuclear magnetic resonance spectroscopy are reviewed.
authors.affiliation: Department of Chemistry, Brandeis University, Waltham, Massachusetts 02454-9110, USA. pochapsk@brandeis.edu
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Pochapsky
authors.forename: Sophia
authors.initials: S
authors.lastname: Kazanis
authors.forename: Marina
authors.initials: M
authors.lastname: Dang
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000201:enzymology* / Q000378:metabolism; D013058:Mass Spectrometry; D019906:Nuclear Magnetic Resonance, Biomolecular; D011387:Prokaryotic Cells / Q000201:enzymology* / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D003577:Cytochrome P-450 Enzyme System
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