Intermediates in P450 catalysis.

Thomas L Poulos

doi:10.1098/rsta.2004.1537

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Intermediates in P450 catalysis.

Thomas L Poulos

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Abstract

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.

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Binding Sites Biopolymers Catalysis Cytochrome P-450 Enzyme System Models, Chemical Models, Molecular Oxidation-Reduction Oxygen Protein Conformation Structure-Activity Relationship Journal Article Review

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Thomas L Poulos. 2005-04-15. Intermediates in P450 catalysis.. https://doi.org/10.1098/rsta.2004.1537

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