The department deals with a study of various enzymes with the purpose of elucidating of catalytic mechanisms as well as peculiarities of the enzymes activity control. The department includes the laboratory of NAD-dependent dehydrogenases (Prof. N.K. Nagradova).

In the group of Prof. V.Muronetz an experimental support has been recently obtained for the hypothesis proposed in this laboratory on the role of specific enzyme-enzyme interactions in the control of the level of 2,3-bisphosphoglycerate in erythrocytes. The pH-dependent variations in the concentrations of this allosteric effector of hemoglobin were shown to originate from the pH-dependent association between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and 2,3-diphosphoglycerate mutase (at pH 6.5) or between GAPDH and 3-phosphoglycerate kinase (at pH 8.0).

Dr. E.Schmalhausen (group of Prof. N.Nagradova) has shown that nonphosphorylating dehydrogenase activity appears upon incubation the GAPDH in the presence of micromolar concentration of hydrogen peroxide. Low molecular thiols have been found to block this activity completely. Therefore the conditions have been discovered for the uncoupling of glycealdehyde-3-phosphate oxidation and phosphorylation in glycolysis.

A special subject is connected with a study of chaperones function in the folding and assembling of oligomeric enzymes and creation of artificial chaperones on the basis of monoclonal antibodies against denatured enzyme forms (the group of Prof.V.Muronetz).

In the group of Prof. G.Kochetov the basic principles of the mechanism of catalytic action of transketolase have been formulated, basing on own data as well as those obtained from the literature. The study of the enzyme is going on with the use of kinetic approaches together with the method of site-specific mutagenesis (collaborative work with Sweden scientists).

Among the subjects of the Department there are a study of complicated polyenzyme complexes of a-ketoacids dehydrogenases. In the group of Prof. L.Khailova control mechanisms of pyruvate dehydrogenase complex is studying with the use of monoclonal antibodies against active sites of the component of the polyenzyme complex together with the methods of site-specific mutagenesis. In the group of Dr. V.Bunik a catalytic mechanism of a-ketoglutarate dehydrogenase is investigating. In collaboration with German scientists the enzyme has been shown to be a target for mitochondrial thioredoxin.

1. Fokina K., Dainyak M., Nagradova N., Muronetz V.I. Arch.Biochem.Biophys. (1997) 345, 185-192.

2. Schmalhausen E.V., Muronetz V.I., Nagradova N.K. FEBS Lett. (1997) 414, 247-252.

3. Kovina M.V., Selivanov V.A., Kochevova N.V., Kochetov G.A. FEBS Lett. (1997) 418, 11-14.

4. Kochetov G.A. Transketolase. Sov. Sci. Rev. D. Physicochem. Biol. Rev. (Ed. V.P.Skulachev), Harwood.Acad.Publ. (1994) 12, 1-73.

5. Bunik V., Follmann H., Bisswanger, H. Activation of mitochondrial 2-oxoacid dehydrogenases by thioredoxin. Biol. Chem. (1997) 378, 1125-1130.