PMID: 6986372Feb 25, 1980Paper

The role of zinc-bound water in liver alcohol dehydrogenase catalysis.

The Journal of Biological Chemistry
S A Evans, J D Shore

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 discus...Continue Reading

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.