Insights into the hydrogen-abstraction reactions of diol dehydratase: relevance to the catalytic mechanism and suicide inactivation

Journal of the American Chemical Society
Gregory M SandalaLeo Radom

Abstract

High-level quantum chemistry calculations have been used to examine the hydrogen-abstraction reactions of diol dehydratase (DDH) in the context of both the catalytic mechanism and the enzyme dysfunction phenomenon termed suicide inactivation. The barriers for the catalytic hydrogen-abstraction reactions of ethane-1,2-diol and propane-1,2-diol are examined in isolation, as well as in the presence of various Brønsted acids and bases. Modest changes in the magnitudes of the initial and final abstraction barriers are seen, depending on the strength of the acid or base, and on whether these effects are considered individually or together. The most significant changes (ca. 20 kJ mol(-1)) are found for the initial abstraction barrier when the spectator OH group is partially deprotonated. Kinetic isotope effects including Eckart tunneling corrections (KIEs) have also been calculated for these model systems. We find that contributions from tunneling are of a magnitude similar to that of the contributions from semiclassical theory alone, meaning that quantum effects serve to significantly accelerate the rate of hydrogen transfer. The calculated KIEs for the partially deprotonated system are in qualitative agreement with experimentally de...Continue Reading

References

Mar 22, 1976·Biochemical and Biophysical Research Communications·T TorayaS Fukui
Sep 30, 2004·Journal of the American Chemical Society·Gregory M SandalaLeo Radom
Jun 16, 2005·Journal of the American Chemical Society·Gregory M SandalaLeo Radom

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Citations

Nov 26, 2013·Archives of Biochemistry and Biophysics·Tetsuo Toraya
Apr 21, 2012·Biochimica Et Biophysica Acta·E Neil G Marsh, Gabriel D Román Meléndez
Mar 28, 2009·Chemistry : a European Journal·Gregory M SandalaLeo Radom
Mar 2, 2010·Chembiochem : a European Journal of Chemical Biology·E Neil G MarshLei Li
Sep 4, 2008·Chembiochem : a European Journal of Chemical Biology·Antonio J PierikJános Rétey
Jun 18, 2009·The Journal of Organic Chemistry·Ruth I J AmosBrian F Yates
Feb 9, 2010·Accounts of Chemical Research·Gregory M SandalaLeo Radom
Apr 2, 2021·Chemistry : a European Journal·Luka BilićBorislav Kovačević
Mar 7, 2021·Journal of Industrial Microbiology & Biotechnology·Yuxuan YeTodd K Hyster
Jun 30, 2019·The Journal of Physical Chemistry. B·Luka BilićBorislav Kovačević
Nov 30, 2018·The Journal of Physical Chemistry. a·Rubik AsatryanEli Ruckenstein

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