title: Closely related isozymes of alcohol dehydrogenase. Carboxymethylation: gamma 1 gamma 1 differs widely from both beta 1 beta 1 and its equine equivalence EE.
abstract: 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.
authors.affiliation: Department of Chemistry I, Karolinska Institutet, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Johansson
authors.forename: B L
authors.initials: BL
authors.lastname: Vallee
authors.forename: H
authors.initials: H
authors.lastname: Jörnvall
mesh_terms: D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D000818:Animals; D001665:Binding Sites; D002021:Buffers; D002264:Carboxylic Acids / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D006736:Horses; D007461:Iodoacetates; D019807:Iodoacetic Acid; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry*; D008745:Methylation; D015032:Zinc / Q000737:chemistry
chemical_list: D002021:Buffers; D002264:Carboxylic Acids; D007461:Iodoacetates; D007527:Isoenzymes; D000426:Alcohol Dehydrogenase; D015032:Zinc; D003545:Cysteine; D019807:Iodoacetic Acid