A low-barrier hydrogen bond in the catalytic triad of serine proteases.
Spectroscopic properties of chymotrypsin and model compounds indicate that a low-barrier hydrogen bond participates in the mechanism of serine protease action. A low-barrier hydrogen bond between N delta 1 of His57 and the beta-carboxyl group of Asp102 in chymotrypsin can facilitate the formation of the tetrahedral adduct, and the nuclear magnetic resonance properties of this proton indicate that it is a low-barrier hydrogen bond. These conclusions are supported by the chemical shift of this proton, the deuterium isotope effect on the chemical shift, and the properties of hydrogen-bonded model compounds in organic solvents, including the hydrogen bond in cis-urocanic acid, in which the imidazole ring is internally hydrogen-bonded to the carboxyl group.
Frey
P A
PA
Institute for Enzyme Research, Graduate School, University of Wisconsin at Madison 53705.
Whitt
S A
SA
Tobin
J B
JB
D001224:Aspartic Acid / Q000737:chemistry; D002384:Catalysis; D002918:Chymotrypsin / Q000737:chemistry* / Q000378:metabolism; D006639:Histidine / Q000737:chemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008298:Maleates / Q000737:chemistry; D008314:Malonates / Q000737:chemistry; D012694:Serine / Q000737:chemistry; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature; D014560:Urocanic Acid / Q000737:chemistry
D008298:Maleates; D008314:Malonates; D001224:Aspartic Acid; D012694:Serine; D006639:Histidine; C087784:2,2-dimethylmalonic acid; C030272:maleic acid; D012697:Serine Endopeptidases; D002918:Chymotrypsin; D014560:Urocanic Acid