title: [Functional role of histidine residues of alpha-ketoglutarate dehydrogenase].
abstract: The protective effect of alpha-ketoglutarate dehydrogenase substrate and its analogs on the enzyme inactivation by diethylpyrocarbonate was studied. The values of true rate constants for diethylpyrocarbonate-induced inactivation and the Kd values for the enzyme complexes with ligands were determined. A comparison of Kd values for a number of ligands suggests that the histidine residue of the enzyme active center interacts with the alpha-keto group of the substrate. A mechanism of this histidine residue involvement in the catalytic act is proposed. According to this mechanism, the imidazole ring of histidine which is responsible for the substrate activation causes a simultaneous formation of a catalytically active form of the coenzyme--thiamine pyrophosphate ilide. It is assumed that the lower (as compared with the enzyme-substrate complexes) values of rate constants of inactivation by diethylpyrocarbonate for alpha-ketoglutarate dehydrogenase complexes with succinate, glutarate, and oxaloacetate are due to additional protonation of the histidine residue, eventually resulting in the blocking of the analogs interaction with the coenzyme.
authors: V I
authors: VI
authors: Bunik
authors: V S
authors: VS
authors: Gomazkova
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology; D006639:Histidine / Q000378:metabolism*; D066298:In Vitro Techniques; D007655:Ketoglutarate Dehydrogenase Complex / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D007700:Kinetics; D013379:Substrate Specificity
chemical_list: D006639:Histidine; D007658:Ketone Oxidoreductases; D007655:Ketoglutarate Dehydrogenase Complex; D004047:Diethyl Pyrocarbonate
vernacular_title: O funktsional'noĭ roli gistidinovykh ostatkov alpha-ketoglutaratdegidrogenazy.