Conformational lock of glucoso-6-phosphatedehydrogenase dimer

It was established that yeast glucoso-6-phosphatedehydrogenase (G6PDH) in s olutions occurs in the form of an equilibrium mixture of dimers and tetrame rs. The dissociation equilibrium constant was calculated from the dependenc e of the specific activity of G6PDH on the initial concentration of the pro tein in the solution by taking into account the fact that the dimer is the only active form of the protein. The specific activity of dimers and the eq uilibrium constant for the dissociation of tetramers at various temperature s were determined. It was shown that the structure of the G6PDH dimer is st able in solution and is maintained by a multiple-point intersubunit contact , the so-called conformational lock. According to a step-by-step mechanism of thermal inactivation of G6PDH, the rupture of one of these contacts resu lts in the formation of a labile form and the establishment of an equilibri um between monomers and dimers of the protein. Computer simulations showed that curves with a maximum in the catalytic activity occur only if the rate constant of dissociation of tetramers k(2) is by an order of magnitude hig her than that of labile dimers k(1).