The main directions of research include studies of enzymatic mechanism of phosphoryl transfer, using genetic engineering, X-ray crystallographic and physico-chemical approaches, and chemical synthesis of biopolymer analogs with directed action.

The crystal structure of free and metal ion- and sulfate-complexed cytoplasmic pyrophosphatase of Escherichia coli and of its several mutant forms was determined (Prof. S.M. Avaeva and co-workers in cooperation with Prof. E. G. Harutyunyan of the Institute of Crystallography). This structure is used as the basis for the substitutions of key amino acid residues in active site and subunit interface in order to understand enzyme mechanism and the role of quaternary structure in catalysis.

Pyrophosphatase was shown to belong to a new class of metal-dependent enzyme whose catalysis requires 3/4 magnesium ions per active site (Prof. A. A. Baykov and co-workers). Studies of membrane proton-translocating pyrophosphatase are under way to understand the molecular mechanism of the coupling of ion transfer across membrane with the synthesis and hydrolysis of high-energy polyphosphates.

Design of enzyme inhibitors acting by disrupting enzyme quaternary structure is one of the goals of future studies. Design and synthesis of new "antisense" agents, basing on nucleoamino acids, and of photoactivated affinity reagents containing trifluoromethyldiazirine group for studies of protein-protein and protein-nucleic acid interactions is carried out by Dr. G.A. Korshunova and co-workers.

1. Cooperman B.S., Baykov A.A. and Lahti R. Evolutionary conservation of the active site of soluble inorganic pyrophosphatase. TIBS (1992) 17, 262-266.

2. Baykov A.A., Dudarenkov V.Ju., Kpyl J., Hyyti T., Kasho V. N., Husgafel S., Cooperman B.S., Goldman A. and Lahti R. Dissociation of hexameric inorganic pyrophosphatase of Escherichia coli into trimers on Hi136®Gln and His140®Gln substitution and its effect on enzyme catalytic properties. J. Biol. Chem. (1995) 270, 30804-30812.

3. Harutyunyan E.H., Oganessyan V.Yu., Oganessyan N.N., Avaeva S.M., Nazarova T.I., Vorobyeva N.N., Kurilova S.A., Huber R., and Mather TThe crystal structure of holo inorganic pyrophosphatase from Escherichia coli at 1.9 A resolution. The mechanism of hydrolisis. Biochemistry, . (1997) 36, 7754-7760.

4. Fabrichniy, I.P., Kasho, V.N., Hyytia, T., Salminen, T., Halonen, P., Dudarenkov, V.Yu., Heikinheimo, P., Chernyak, V.Ya., Goldman, A., Lahti, R., Cooperman, B.S., and Baykov, A.A. Structural and functional consequences of substitutions at the tyrosine 55-lysine 104 hydrogen bond in Escherichia coli inorganic pyrophosphatase. Biochemistry (1997) 36, 7746-7753.

5. Sumbatuan N.V., Gröger K., Chichenkov O.N., and Korshunova G.A. (1977) Synthesis and activity of dermorphin analogues containing unusual amino acid residues. Lett. Pept. Sci. 4, 477-480.