Dissociative thermal inactivation, stability, and activity of oligomeric enzymes.
Results of kinetic studies on dissociative thermal inactivation of oligomeric enzymes are discussed. Dissociative thermal inactivation is the process in which the kinetically irreversible protein change is preceded by a reversible stage of oligomer dissociation. In experiments, this is demonstrated by the dependence of inactivation rate on total protein concentration. This paper gives the relations which allow the calculation from experimental data the following physicochemical constants which characterize the stability of oligomeric enzymes: the constant for the rate of irreversible change of monomeric protein, the equilibrium constant for dimer dissociation, and the rate constant for dimer dissociation. The problem of a "conformational lock", the contact between protein globules that admits a multistep destruction of active oligomer and explains the induction period occurring in kinetic thermal inactivation curves, is discussed. The X-ray structural analyses for several dimeric enzymes, i.e., alkaline phosphatase (EC 3.1.3.1) from E. coli, alcohol dehydrogenase (EC 1.1.1.1) from horse liver, and baker's yeast enolase (EC 4.2.1.11), explain why they lose catalytic activity during the dissociation of the protein into monomers and also provide a physically reasonable picture of the structure of their conformational lock. Also, these data support the kinetic scheme used to describe the dissociative inactivation of dimeric enzymes.
Poltorak
O M
OM
School of Chemistry, Lomonosov Moscow State University, Moscow, 119899 Russia.
Chukhray
E S
ES
Torshin
I Y
IY
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D019281:Dimerization; D004795:Enzyme Stability; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011487:Protein Conformation; D013816:Thermodynamics
D004798:Enzymes; D000426:Alcohol Dehydrogenase; D000469:Alkaline Phosphatase; D010751:Phosphopyruvate Hydratase