Low-barrier hydrogen bonds and enzymic catalysis.
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.
Cleland
W W
WW
Institute for Enzyme Research, University of Wisconsin, Madison 53705.
Kreevoy
M M
MM
D000154:Aconitate Hydratase / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002268:Carboxypeptidases / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D002950:Citrate (si)-Synthase / Q000737:chemistry / Q000378:metabolism; D004798:Enzymes / Q000378:metabolism*; D006860:Hydrogen Bonding; D007535:Isomerases / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000737:chemistry / Q000378:metabolism; D019998:Racemases and Epimerases / Q000737:chemistry / Q000378:metabolism; D013820:Thermolysin / Q000737:chemistry / Q000378:metabolism
D004798:Enzymes; D002950:Citrate (si)-Synthase; D002268:Carboxypeptidases; D013820:Thermolysin; D009964:Orotidine-5'-Phosphate Decarboxylase; D000154:Aconitate Hydratase; D007535:Isomerases; D019998:Racemases and Epimerases; C021540:mandelate racemase