title: Binding of ligands to the catalytic zinc ion in horse liver alcohol dehydrogenase.
abstract: The affinity of nitrogen and sulfur ligands for the catalytic zinc ion in horse liver alcohol dehydrogenase has been investigated by their influence on the affinity labeling reaction with iodoacetate. All the nitrogen compounds including ammonia, a primary and a secondary amine, and heterocycles containing a pyridine-type nitrogen with the exception of 2,2-dipyridyl were found to activate the affinity labeling reaction. Activation results from inner-sphere ligand coordination to the catalytic zinc ion. Closely related pyridine compounds gave a regular increase in affinity for the enzyme with increasing basicity, as expected for coordination to a metal ion. The sulfur compounds penicillamine and mercaptoethanol also activated the affinity labeling reaction, but dimercaptopropanol bound very tightly as a bidentate inhibited the reaction. The anions hydrosulfide, diethyldithiocarbamate, and cyanide coordinated to the catalytic zinc ion, whereas azide, thiocyanate, tetrazole, and iodide complexed the anion-binding site. The anionic metal ligands increased the rate of inactivation of the enzyme with iodoacetamide by binding to the catalytic zinc ion, while the binding of iodoacetate to the anion-binding site was prevented.
mesh_terms: D015082:2,2'-Dipyridyl / Q000378:metabolism; D000345:Affinity Labels / Q000378:metabolism; D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000838:Anions; D006736:Horses; D007460:Iodoacetamide / Q000494:pharmacology; D007461:Iodoacetates / Q000378:metabolism; D019807:Iodoacetic Acid; D008024:Ligands / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D009584:Nitrogen / Q000494:pharmacology*; D013455:Sulfur / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism*
chemical_list: D000345:Affinity Labels; D000838:Anions; D007461:Iodoacetates; D008024:Ligands; D015082:2,2'-Dipyridyl; D013455:Sulfur; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D015032:Zinc; D009584:Nitrogen; D019807:Iodoacetic Acid; D007460:Iodoacetamide