LOW-BARRIER HYDROGEN-BONDS AND ENZYMATIC CATALYSIS

Formation of a short (less than 2.5 angstroms), very strong, low-barri er hydrogen bond in the transition state, or in an enzyme-intermediate complex, can be an important contribution to enzymic catalysis. Forma tion of such a bond can supply 10 to 20 kilocalories per mole and thus facilitate difficult reactions such as enolization of carboxylate gro ups. Because low-barrier hydrogen bonds form only when the pK(a)'s (ne gative logarithm of the acid constant) of the oxygens or nitrogens sha ring the hydrogen are similar, a weak hydrogen bond in the enzyme-subs trate complex in which the pK(a)'s do not match can become a strong, l ow-barrier one if the pK(a)'s become matched in the transition state o r enzyme-intermediate complex. Several examples of enzymatic reactions that appear to use this principle are presented.