Closely related isozymes of alcohol dehydrogenase Carboxymethylation: γ1γ1 differs widely from both β1β1 and its equine equivalence EE

Human gamma 1 gamma 1 alcohol dehydrogenase is quite insensitive to inactivation by iodoacetate, its equine counterpart EE highly sensitive, and the human beta 1 beta 1 form intermediately sensitive. Imidazole hardly influences the iodoacetate inactivation of gamma 1 gamma 1, enhances that of EE and decreases that of beta 1 beta 1. In all isozymes, metal-binding Cys residues are the most reactive, but the patterns for those binding the active site zinc atom differ. In phosphate, Cys-46 is most sensitive in EE and gamma 1 gamma 1, Cys-174 in beta 1 beta 1. This difference appears to correlate with the absence or presence, respectively, of an extra methyl group in the side-chain at position 48 (Ser in EE and gamma 1 gamma 1, Thr in beta 1 beta 1). In imidazole, the reactivity in beta 1 beta 1 is shifted to Cys-46, while the specificity is enhanced in EE and decreased in gamma 1 gamma 1. Thus, the inactivations illustrate large differences among structures closely related.