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Science 24 June 1994:
Vol. 264. no. 5167, pp. 1887 - 1890
DOI: 10.1126/science.8009219
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Articles

Science, Vol 264, Issue 5167, 1887-1890
Copyright © 1994 by American Association for the Advancement of Science

articles

Low-barrier hydrogen bonds and enzymic catalysis

WW Cleland and MM Kreevoy

Institute for Enzyme Research, University of Wisconsin, Madison 53705.

Formation of a short (less than 2.5 angstroms), very strong, low-barrier hydrogen bond in the transition state, or in an enzyme-intermediate complex, can be an important contribution to enzymic catalysis. Formation of such a bond can supply 10 to 20 kilocalories per mole and thus facilitate difficult reactions such as enolization of carboxylate groups. Because low-barrier hydrogen bonds form only when the pKa's (negative logarithm of the acid constant) of the oxygens or nitrogens sharing the hydrogen are similar, a weak hydrogen bond in the enzyme-substrate complex in which the pKa's do not match can become a strong, low-barrier one if the pKa's become matched in the transition state or enzyme-intermediate complex. Several examples of enzymatic reactions that appear to use this principle are presented.


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