Intermediates in P450 catalysis.
Cytochromes P450 catalyse the insertion of one O2-derived oxygen atom in unactivated C-H bonds, and as such, are potent oxidants. A significant amount is known about the P450 catalytic cycle owing partly to the single heme group at the active site that provides spectroscopic handles in tracking various intermediates. A sophisticated array of electron paramagnetic, electron double nuclear resonance, and more traditional absorption spectroscopies have been able to identify key intermediates, while crystallography has defined the structure of the substrate-free, -bound, and oxy-complexes. What has remained elusive is the Fe(IV)=O intermediate, thought to be the active hydroxylating agent. Here, theory and especially density functional calculations have provided valuable insights.
Poulos
Thomas L
TL
Department of Molecular Biology and Biochemistry and the Program in Chemical and Structural Biology, University of California, Irvine, CA 92697-3900, USA. poulos@uci.edu
D001665:Binding Sites; D001704:Biopolymers / Q000737:chemistry*; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D001704:Biopolymers; D003577:Cytochrome P-450 Enzyme System; D010100:Oxygen