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 seri ne protease action. A low-barrier hydrogen bond between N delta 1 of H is(57) and the beta-carboxyl group of Asp(102) in chymotrypsin can fac ilitate the formation of the tetrahedral adduct, and the nuclear magne tic resonance properties of this proton indicate that it is a low-barr ier hydrogen bond. These conclusions are supported by the chemical shi ft of this proton, the deuterium isotope effect on the chemical shift, and the properties of hydrogen-bonded model compounds in organic solv ents, including the hydrogen bond in cis-urocanic acid, in which the i midazole ring is internally hydrogen-bonded to the carboxyl group.