Activation of molecular oxygen in cytochromes P450

Ilia G. Denisov, Stephen G. Sligar

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The complex multistep mechanism of oxygen activation in P450 is reviewed as a sequence of the following reactions: Substrate binding, reduction of the heme iron from ferric to the ferrous state, binding of dioxygen, second electron transfer and formation of peroxo-ferric intermediate, two sequential protonation events to give hydroperoxo-ferric intermediate, and finally, after O–O bond scission, the ferryl-oxo intermediate, termed compound I. Details of these processes and the role of interactions with redox partners, as well as substrate variability in the overall efficiency of P450 catalysis, are discussed. In addition, common points and variations between the soluble prokaryotic and membrane-bound eukaryotic cytochromes P450 with respect to the oxygen activation mechanisms are briefly compared.

Original languageEnglish (US)
Title of host publicationCytochrome P450
Subtitle of host publicationStructure, Mechanism, and Biochemistry, Fourth Edition
PublisherSpringer International Publishing
Pages69-109
Number of pages41
ISBN (Electronic)9783319121086
ISBN (Print)9783319121079
DOIs
StatePublished - Jan 1 2015

Keywords

  • Compound I
  • Compound II
  • Ferrous dioxygen complex (oxy-complex)
  • Hydroperoxo intermediate
  • Mössbauer spectroscopy
  • Nanodiscs
  • Oxygen binding
  • O–O bond
  • Peroxide dissociation
  • Peroxo intermediate
  • Raman (rR)
  • Redox partner
  • Redox potential
  • Resonance
  • Spin shift
  • Substrate binding
  • Superoxide
  • Uncoupling
  • Water ligand

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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  • Cite this

    Denisov, I. G., & Sligar, S. G. (2015). Activation of molecular oxygen in cytochromes P450. In Cytochrome P450: Structure, Mechanism, and Biochemistry, Fourth Edition (pp. 69-109). Springer International Publishing. https://doi.org/10.1007/978-3-319-12108-6_3