Solvent isotope and mutagenesis studies on the proton relay system in yeast alcohol dehydrogenase 1.

ABSTRACT: Alcohol dehydrogenase catalyzes the reversible transfer of a hydride directly from an alcohol to the nicotinamide ring of NAD⁺ to form an aldehyde and NADH, and the proton from the alcohol probably is transferred through a hydrogen-bonded system to the imidazole of His-48. Studies of the pH dependencies, and solvent and substrate isotope effects on the wild-type and the enzyme with His-48 substituted with Gln-48 were used to demonstrate a role for the proton relay system. The H48Q substitution increases affinities for NAD⁺ and NADH by ∼2-fold, suggesting that the overall protein structure is maintained. In contrast, catalytic efficiencies (V/K_m) on ethanol and acetaldehyde and affinity for 2,2,2-trifluoroethanol are decreased by about 10-fold. The pH depend

SUBMITTER: Plapp BV 

PROVIDER: S-EPMC10843573 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature