DEPARTMENT OF ANIMAL CELL BIOCHEMISTRY
Vladimir I. Muronetz
Head of Department, Sc.D., Professor
tel. 007-495-939-1456, fax: 007-495-939-3181. E. mail: vimuronets@belozersky.msu.ru
vimuronets@mail.ru
Department was organized in 1965 by the outstanding Russian biochemist,
brilliant teacher and organizer of the domestic science, Sergei E. Severin.
He was an Academician of Academy of Sciences and Academy of Medical Sciences
of USSR, a member of several foreign Academies, the president of the All-Union
biochemical society, the editor-in-chief of journal "Biochemistry" (Moscow),
and head of chair of biochemistry of biological faculty of the Moscow State
University). S.E. Severin was a head of the department from 1965 to 1988.
During the next years (1988-1996), the department was headed by the professor
G.A. Kochetov. Since 1996, the department has been headed by the senior researcher,
Professor V.I. Muronetz.
The Department includes Laboratory of NAD -dependent dehydrogenases
(Head: Prof. N.K. Nagradova). Leading researchers of the Department: Prof.
G.A. Kochetov, Prof. N.K. Nagradova, Ph.D. R.A. Asriyants, Ph.D. L.E. Meshalkina,
Ph.D. I. N. Naletova, Ph.D. I.A. Sevostyanova, Ph.D. O.N. Solovjeva, Ph.D.
E.V. Schmalhausen)
Basic scientific trends of the Department Investigation of the role
of glyceraldehyde 3-phosphate dehydrogenase in apoptosis and in the development
of some neurodegenerative diseases (head – Prof. V.I. Muronets). Role of
chaperones in the prevention of enzyme’s aggregation. (head – Prof. V.I.
Muronets). Structure, mechanism of action and regulation of thiamin diphosphate
enzymes. (head – Prof. G.A.Kochetov). Studies of the role of energy metabolism
in regulation of mobility of spermatozoa (head – Ph.D. E. V. Schmalhausen).
Participation in Scientific projects and programs. The work was supported
by the Russian Foundation of basic Research ¹ 04-04-81038 "Role of enzyme
oxidation in the development of neurodegenerative diseases and apoptosis
(2004-2006, V.I. Muronets), ¹ 05-04-48955 « Mechanisms of aggregation, denaturation,
and chaperone-dependent folding of dehydrogenases – thermodynamic analysis
and molecular modeling» (2005-2007, V.I. Muronets), ¹ 06-04-48240 «Role of
energy metabolism in regulation of mobility of spermatozoa» (2006-2008, E.
V. Schmalhausen); ¹ 06-04-48395 ” Structure of the transketolase active center
and the kinetic mechanism of the enzyme functioning” (2006-2007, G.A. Kochetov).
The work was supported by the grant of the President of Russian Federation
for young scientists ¹ MK 3368.2005.4 “New form of transketolase specific
for cancer tissue”. The work was supported by the international grants INTAS
(GRANT 03-51-4813, 2004-2007 «Mechanisms of protein denaturation and design
of new inhibitors of protein aggregation for the pharmacological treatment
of Alzheimer and other condensation diseases") and NATO (2004-2007). These
scientific programs are carried out in collaboration with Chair of pharmacology
of Rome University (project coordinator, Prof. Luciano Saso), France, Sweden,
Belorussia, and Russia (A.N. Bach Institute of Biochemistry RAS); Since 1996,
the scientific joint program has been carried out in collaboration with
the laboratory of enzymology of University of Nancy (France) and the laboratory
headed by Prof. T. Haertle (Nantes, France).
Main scientific achievements of the department: The hypothesis of uncoupling
of oxidation and phosphorylation in glycolysis by mild oxidation of GAPDH
in the presence of hydrogen peroxide was suggested and proved [Schmalhausen,
Muronetz, 1997; Schmalhausen et al., 1997]. A system of artificial chaperone
based on the immobilized antibodies against denatured enzymes has been developed.
[Muronetz et al., 2000]. It was demonstrated that oxidation of glyceraldehyde-3-phosphate
dehydrogenase results in translocation of the enzyme from the cytoplasm into
the nucleus, this inducing to apoptosis of the cells [Arutyunova et al.,
2003]. It was shown that the irreversible inhibition of chaperones by modified
forms of enzymes could play an important role in the development of neurodegenerative
dieses [Polyakova et al, 2005, Naletova et al, 2006]. The catalytic active
N1’H- imino tautomeric form of the coenzyme thiamin diphosphate was identified
in the active center of transketolase [Kovina et al. 2002]; it was shown
that apart from catalyzing the common two-substarte reaction, transketolase
is able to catalyze a one- substrate reaction, using only ketose (xylulose
5-phosphate) or only aldose (glycolaldehyde) as the substrate [Bykova et
al, 2001], [Sevostyanova et al, 2005].
Scientific rewards: “Lenin’s Reward” (S.Å. Severin), two “Government
rewards” (G.À. Kochetov, N.K. Nagardova), the first reward of Ministry of
Institutes of Higher Education of USSR for the best scientific work (G.À.
Kochetov), two rewards of European Academy of Science for young scientists
(E. V. Schmalhausen, M.V. Kovina), two A.D. Kaulen’s rewards for young scientists
of Moscow State University (I. A. Sevostyanova, O.N. Ivinova).
Teaching: Researchers of the department are engaged in teaching at School
of Bioengineering and Bioinformatics and at School of Biology (Chair of Biochemistry)
of Moscow State University. Professors N. K. Nagradova and V.I. Muronets
give courses of lectures. Researchers of the department are also involved
in managing of degree theses of post-graduate students. There are 4 Ph.D
students and 4 graduate students are working at the department. Since 2003,
4 Ph.D theses have been defended by the Ph.D students of the department.
Selected publications:
1. Roitel O, Ivinova O, Muronetz V, Nagradova N, Branlant G. Thermal unfolding
used as a probe to characterize the intra- and intersubunit stabilizing interactions
in phosphorylating D-glyceraldehyde-3-phosphate dehydrogenase from Bacillus
stearothermophilus. Biochemistry. 2002; 41: 7556-7564.
2. Kovina MV, Bykova IA, Solovjeva ON, Meshalkina LE, Kochetov GA. The
origin of the absorbtion band induced through the interaction between apotransketolase
and thiamin diphosphate. Biochem Biophys. Res Commun. 2002; 294: 155-160.
3. Êî÷åòîâ Ã.À. Functional flexibility of the Transketolase molecule.
Biochemistry (Moscow) 2001; 66: 1335-1345.
4. Bykova IA, Solovjeva ON, Meshalkina LE, Kovina MV, Kochetov GA. One-substrate
transketolase-catalyzed reaction. Biochem Biophys Res Commun. 2001; 280:
845-847.
5. Muronetz VI, Kazakov SV, Dainiak MB, Izumrudov VA, Galaev IY, Mattiasson
B. Interaction of antibodies and antigens conjugated with synthetic polyanions:
on the way of creating an artificial chaperone. Biochim Biophys Acta. 2000;
1475: 141-150.
6. Schmalhausen EV, Muronetz VI. An uncoupling of the processes of oxidation
and phosphorylation in glycolysis. Biosci Rep. 1997; 17: 521-527.
6. Schmalhausen EV, Muronetz VI, Nagradova NK. Rabbit muscle GAPDH: non-phosphorylating
dehydrogenase activity induced by hydrogen peroxide. FEBS Lett. 1997; 414:
247-252.
7. Fokina KV, Dainyak MB, Nagradova NK, Muronetz VI. A study on the complexes
between human erythrocyte enzymes participating in the conversions of 1,3-diphosphoglycerate.
Arch Biochem Biophys. 1997; 345: 185-192.
8. Kochetov GA. Transketolase from yeast, rat liver and pig liver. Methods
Enzymol. 1982; 90: 209-223.
9. Nagradova NK, Ashmarina LI, Asryants RA, Cherednikova TV, Golovina
TO, Muronetz VI. Glyceraldehyde-3-phosphate dehydrogenase: the role of subunit
interactions in enzyme functioning. Adv Enzyme Regul. 1980; 19: 171-204.
10. Meshalkina LE, Kochetov GA. The functional identity of the active
centers of transketolase. Biochim Biophys Acta. 1979; 571: 218-223.
11. Nagradova NK, Asryants RA, Benkevich NV. The role of arginine residues
in the function of D-glyceraldehyde-3-phosphate dehydrogenase. Biochim Biophys
Acta. 1978; 527: 319-326.
12. Muronetz VI, Golovina TO, Nagradova NK. Rat skeletal muscle glyceraldehyde-3-phosphate
dehydrogenase: adenine nucleotide-induced inactivation. Arch Biochem Biophys.
1976; 177: 16-23.
Some publications since 2004:
1. Arutiunova, E.I., Pleten, A.P., Nagradova, N.K., Muronetz, V.I. Antibodies
to inactive conformations of glyceraldehyde-3-phosphate dehydrogenase inactivate
the apo- and holoforms of the enzyme. Biochemistry (Moscow), 2006, 71(6),
847 –855.
2. Ospanov, R., Kochetov, G., Kurganov, B. Influence of donor substrate
on kinetic parameters of thiamine diphosphate binding to transketolase. Biochemistry
(Moscow), 2007, 72, 100-109.
3. Ospanov, R., Kochetov, G., Kurganov, B. Theoretical model of interactions
between ligand-binding sites in a dimeric protein and its application for
the analysis of thiamine diphosphate binding to yeast transketolase. Biophys.
Chem., 2006, 124, 106-114.
4. Esakova, O.A., Khanova, E.A., Meshalkina, L.E., Golbik, R., Hubner,
G., Kochetov, G.A. Effect of transketolase substrates on holoenzyme reconstitution
and stability. Biochemistry (Moscow), 2005, 70 770-776.
5. Shalova I.N., Cechalova K., Rehakova Z., Dimitrova P., Ognibene E.,
Caprioli A., Schmalhausen E.V., Muronetz V.I., Saso L. Decrease of dehydrogenase
activity of cerebral glyceraldehyde-3-phosphate dehydrogenase in different
animal models of Alzheimer s disease. Biochim. Biophys. Acta. 2007 (accepted,
in press).
6. Khanova E.A., Markossian K.A., Kleimenov S.Y., Levitsky D.I., Chebotareva
N.A., Asryants R.A., Muronetz V.I., Saso L., Yudin I.K., Muranov K.O., Ostrovsky
M.A., Kurganov B.I. Effect of α-crystallin on thermal denaturation and aggregation
of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase. Biophysical Chemistry,
2007, 125(2-3), 521-531.
7. Markossian K.A., Khanova H.A., Kleimenov S.Y., Levitsky D.I., Chebotareva
N.A., Asryants R.A., Muronetz V.I., Saso L., Yudin I.K., Kurganov B.I. Mechanism
of Thermal Aggregation of Rabbit Muscle Glyceraldehyde-3-phosphate Dehydrogenase.
Biochemistry. 2006, 45(44),13375-13384.
8. K.A. Markossian, B.I. Kurganov, D.I. Levitsky, H.A. Khanova, N.A. Chebotareva,
A.M. Samoilov, T.B. Eronina, N.V. Fedurkina, L.G. Mitskevich, A.V. Merem'yanin,
S.Yu. Kleymenov, V.F. Makeeva, V.I. Muronetz, I.N. Naletova, I.N. Shalova,
R.A. Asryants, E.V. Schmalhausen, L. Saso, Yu.V. Panyukov, E.N. Dobrov, I.K.
Yudin, A.C. Timofeeva, K.O. Muranov, and M.A.Ostrovsky. Mechanism of chaperone-like
activity. "Protein Folding: New Research". Nova Science Publishers, Inc.,
New York, USA, 2006, 89-173.
9. Arutiunova, E.I., Pleten, A.P., Nagradova, N.K., Muronetz, V.I. Antibodies
to Inactive Conformations of Glyceraldehyde-3-phosphate Dehydrogenase Inactivate
the Apo- and Holoforms of the Enzyme. Biochemistry (Mosc), 2006, 71(6), 685-691.
10. Naletova, I.N., Muronetz, V.I., Schmalhausen, E.V. Unfolded, oxidized,
and thermoinactivated forms of glyceraldehyde-3-phosphate dehydrogenase interact
with the chaperonin GroEL in different ways, BBA (Proteins and Proteomics),
2006, 1764(4):831-838.
11. Shalova I.N. , Asryants R.A., Sholukh M.V., Saso L., Kurganov B.I.,
Muronetz V.I., Izumrudov V.A. Interaction of Polyanions with Basic Proteins,
2 Influence of Complexing Polyanions on the Thermoaggregation of Oligomeric
Enzymes Macromol. Biosci. 2005, 5, 1184–1192.
12. Golbik, R., Meshalkina, L.E., Sandalova, T., Tittman, K., Fiedler,
E., Neef, H., König, S., Kluger, R., Kochetov, G.A., Schneider, G., Hübner,
G. Effect of coenzyme modification on structural and catalytic properties
of transketolase wildtype and the variant E418A from Saccharomyces cerevisiae.
FEBS Journal 272 (2005) 1326-1342.
13. Esakova, O.A., Meshalkina, L.E., Kochetov, G.A. Effects of transketolase
cofactors on its conformation and stability. Life Science 78 (2005) 8-13.
14. Kochetov, G.A., Sevostyanova, I.A. Binding of the coenzyme and formation
of the transketolase active center. IUBMB Life 57 (2005) 491-497.
15. Selivanov, V.A., Meshalkina, L.E.,Solovjeva, O.N., Kuchel, P., Ramos-Montoya,
A., Kochetov, G.A., Lee, P., W., N., Cascante, M. Rapid simulationand analysis
of isotopomer distributions using constraints based on enzyme mechanisms:
an example from HT29 cancer cells. Bioinformatics, 21 (2005) 3558-3564.
16. Rahuel-Clermont S, Arutyunov D, Marchal S, Orlov V, Muronetz V, Branlant
G. Thermal destabilization of non-phosphorylating glyceraldehyde-3-phosphate
dehydrogenase from Streptococcus mutans upon phosphate binding in the active
site. J Biol Chem. 2005; 280(19):18590-18597.
17. Polyakova OV, Roitel O, Asryants RA, Poliakov AA, Branlant G, Muronetz
VI. Misfolded forms of glyceraldehyde-3-phosphate dehydrogenase interact
with GroEL and inhibit chaperonin-assisted folding of the wild-type enzyme.
Protein Sci. 2005;14(4):921-928.
18. Arutyunova EI, Arutyunov DY, Pleten' AP, Nagradova NK, Muronetz VI.
Antibodies specific to modified glyceraldehyde-3-phosphate dehydrogenase
induce inactivation of the native enzyme and change its conformation. Biochim
Biophys Acta. 2004 Jul 1;1700(1):35-41.
19. Schmalhausen, E.V., Pleten', A.P., Muronetz, V.I. Ascorbate-induced
oxidation of glyceraldehyde-3-phosphate dehydrogenase. Biochem. Biophys.
Res. Commun. 2003, 308(3), 492-496.
20. Arutyunova, E.I., Danshina, P.V., Domnina, L.V., Pleten’, A.P., Muronetz,
V.I. Oxidation of glyceraldehyde-3-phosphate dehydrogenase enhances its binding
to nucleic acids. Biochem. Biophys. Res. Commun. 2003, 307(3), 547-552.
21. Pushkin A, Abuladze N, Newman D, Muronets V, Sassani P, Tatishchev
S, Kurtz I. The COOH termini of NBC3 and the 56-kDa H+-ATPase subunit are
PDZ motifs involved in their interaction. Am J Physiol Cell Physiol. 2003;
284: 667-73.
22. Muronetz VI, Korpela T. Isolation of antigens and antibodies by affinity
chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2003; 790:
53-66.
23. Arutyunov DY, Muronetz VI. The activation of glycolysis performed
by the non-phosphorylatingglyceraldehyde-3-phosphate dehydrogenase in the
model system. Biochem Biophys Res Commun. 2003; 300: 149-154.
24. Dan'shina, P.V., Schmalhausen, E.V., Arutiunov, D.Y., Pleten', A.P.,
Muronetz,V.I. Acceleration of glycolysis in the presence of the non-phosphorylating
and the oxidized phosphorylating glyceraldehyde-3-phosphate dehydrogenases.
Biochemistry (Moscow) 2003; 68: 725-33.