The role of zinc-bound water in liver alcohol dehydrogenase catalysis.
Year: 1980
Type: article
Abstract: To elucidate the role of zinc-bound water in liver alcohol dehydrogenase catalysis, chelation by 1,10-phenanthroline and 2,2-bipyridine was studied. The rate constants for association of both chelating agents to the active center zinc were pH-dependent with a pKa of 9.2 and preferential binding to a protonated form. The binary complex dissociation rate constants were pH-independent for both chelating agents. In the presence of saturating NAD+, the pKa for the equilibrium binding of 2,2-bipyridine was perturbed to 7.6, similar to the functional group previously shown to be involved in NAD+ binding. The presence of saturating imidazole resulted in pH-independent 2,2-bipyridine binding. These studies provide compelling evidence that the ionizing enzyme functional group involved in coenzyme binding, proton liberation, and conformational states is zinc-bound water. The limiting rate of chelation by 2,2-bipyridine was pH-independent, and no limiting rate was observed in the presence of saturating imidazole. These results indicate that the limiting rate of chelation is due to the rate of dissociation of zinc-bound water. The implications of this regarding the role of zinc in catalytic turnover of liver alcohol dehydrogenase are discussed.
Source: Journal of Biological Chemistry
Authors: S.A. Evans, J.D. Shore
Institution: Henry Ford Hospital
Language: English
Topic: Chemical Reaction Mechanisms
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1599344936