BY THOMAS L. POULOS Departments of Molecular Biology and Biochemistry, Physiology

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)aO intermediate, thought to be the active hydroxylating agent. Here, theory and especially density functional calculations have provided valuable insights