Proton transfer in mechanistic enzymology: Key steps in oxygen activation by the cytochrome P-450 monoxygenases

Research output: Contribution to journalArticlepeer-review

Abstract

The vasl array of biological oxidations that catalyze chemical transformations involve a net gain or loss of both protons and electrons. Although recent research into the precise physical mechanism of protein electron transfer suggests that in some cases there may exist "wired" structures in this phase of condensed matter, in most biochemical process Nature chooses to regulate and control the proton rather than the electron. Key steps in oxygen activation by the P-450 monoxygenases to form iron cooridnated dioxygen complexes one or two elctrons reduced from the ferric home resting state, or a committment to electrophilic or radical catalysis through .oxygen-oxygen bond scission requires precise control of proton transfer events. Using a combination of rapid reaction methodologies, isotope effects, and site directed mutagenesis, William Atkins, Nancy Gerber, Moma Vidakovic, and David Benson in our laboratory have contributed to the identification of proton control points and pathways in the P-450 reaction cycle. Through collaboration with Dr. lime Schleting, x-ray structures of native and mutant enzyme have yielded a picture of the quasi stable intermediates that are linked by these electron and proton transfer events. In my lecture, 1 will summarize the nature of biological proton transfer catalysis and present our integrated picture of oxygen activation with a focus on the energeiics and dynamics of hydrogen bonding events. Our research is supported hv the National Institutes of Health.

Original languageEnglish (US)
Pages (from-to)A773
JournalFASEB Journal
Volume11
Issue number9
StatePublished - 1997

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry
  • Biotechnology

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