TY - JOUR
T1 - Proton transfer in mechanistic enzymology
T2 - Key steps in oxygen activation by the cytochrome P-450 monoxygenases
AU - Sugar, S. G.
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
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M3 - Article
AN - SCOPUS:33750100232
SN - 0892-6638
VL - 11
SP - A773
JO - FASEB Journal
JF - FASEB Journal
IS - 9
ER -