How a Single-Point Mutation in Horseradish Peroxidase Markedly Enhances Enantioselectivity
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Klibanov_How a single-point.pdf
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Author(s)
Antipov, Eugene
Cho, Art E.
Klibanov, Alexander M.
Date Issued
August 2009
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society
Citation
Antipov, Eugene, Art E. Cho, and Alexander M. Klibanov. “How a Single-Point Mutation in Horseradish Peroxidase Markedly Enhances Enantioselectivity.” Journal of the American Chemical Society 131, no. 31 (August 12, 2009): 11155-11160.
Version
Author's final manuscript
Abstract
The effect of all possible mutations at position 178 on the enantioselectivity of yeast surface-bound horseradish peroxidase (HRP) toward chiral phenols has been investigated. In contrast to their wild-type predecessor, most HRP mutants are enantioselective, with the Arg178Glu variant exhibiting the greatest, 25-fold, (S)/(R) preference. Using kinetic analysis of enzymatic oxidation of various substrate analogues and molecular modeling of enzyme−substrate complexes, this enantioselectivity enhancement is attributed to changes in the transition state energy due to electrostatic repulsion between the carboxylates of the enzyme’s Glu178 and the substrate’s (R)-enantiomer.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1021/ja903482u
