Stabilization Mechanism of Glucose-6-phosphate Dehydrogenase
نویسندگان
چکیده
Yeast glucose-6-phosphate dehydrogenase (G6PDH) in solutions exists as the equilibrium mixture of dimers and tetramers. Only dimers are active. The equation responding to these conditions was used to determine the parameters: the specific activity of dimers and the dissociation equilibrium constant of tetramers. The stability of G6PDH dimers were shown to be maintained due to the conformational lock, a multiple-point intersubunit contact in the hydrophobic region of “cylindrical” protomers. The conformational lock is formed by two isolated contacts at least. In the consecutive mechanism of G6PDH thermal inactivation, the destruction of one of these contacts results in a labile dimer. The latter dissociates to inactive monomers. At 46◦C, the equilibrium constant of this process K dis = (6.2± 0.4) nM, whereas the specific activity dimers a2 = (13 ± 0.2) × 10 mol NADPH/min.mol of active sites. The kinetic analysis showed that the inactivation process is preceded by tree steps: the dissociation of tetramers to active stable dimers, the emergence of labile dimers and their dissociation to inactive protomers. The final step of G6PDH thermal inactivation is an irreversible inactivation of protomers, the denaturation with the rate constant k = 6× 10−3 min−1 .
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