TUKALO
Mikhailo Arsentiyovich
українська версія
Date of birth: June 2, 1951.
Degree: Taras Shevchenko Kyiv National University, M.S. in Biochemistry
(1968-1973).
Dsc in Molecular Biology,
year awarded: 1989.
Degrees: Senior Researcher,
year awarded: 1988.
Place of work: Institute of Molecular Biology and Genetics NAS of Ukraine.
Present position: Head of Department of Protein Synthesis Enzimology.
Honours and awards:
1986, State Prize of Ukraine in Science and Technique for contribution to
Molecular Biology through research on the regulation of protein
biosynthesis.
Grants:
1992-1995, NATO Collaborative Research Grant;
1995-2000, Howard Hughes Medical Institute International Research Grant;
2001-2003, INTAS Collaborative Research Grant.
My general research interest is the structural basis of the RNA- protein
recognition and enzymatic catalysis. The research of the last years is
directed at the identification of the structural bases of the decoding of
genetic information. The current area of focus is the specific recognition
of aminoacyl-tRNA synthetases (aaRSs) for their cognate amino acid and tRNA,
mechanisms of catalysis and editing. Using biochemical methods,
site-directed mutagenesis and X-ray crystallography, work carried out on
different prokaryotic (including important pathogenic bacteria Enterococcus
faecalis, Mycobacterium tuberculosis and Streptococcus pneumoniae),
eukaryotic and archaeal systems.
In collaboration with Dr. S. Cusack (the European Molecular Biological
Laboratory) the dimensional structures of several aaRSs and their complexes
with various combinations of substrata, including the tRNA complexes, are
being studied. The synthesis of specific products by aaRSs has been shown to
be accompanied by the conformational changes both in the active centre of
enzyme and beyond. The data obtained allowed to understand the mechanism of
amino acids activation and the molecular mechanism of the recognition of
homologous tRNA and their aminoacylation by these enzymes.
The best progress has been made on the seryl-, tyrosyl- and leucyl- tRNA
synthetases from Thermus thermophilus, which in prokaryotes can recognise
tRNA with a long variable arm. The determination of a complex of SerRs and
tRNA Ser provided the first information on the structure of a tRNA with a
long variable arm and elucidated the details of how enzyme interacts with
tRNA. As a result of solving the structure of TyrRS for the first time an
unusual for these enzymes type recognition of tRNA has been demonstrated.
Tyrosyl-tRNA synthetase belongs to the first structural class, but its type
of recognition is specific for the class 2 aaRSs, where tRNA interacts with
an enzyme from the side of a long variable arm. Finally, after the structure
of a complex of the leucyl-tRNA synthetase with tRNALeu was determined, a
full picture of the interaction of the synthetases with tRNA, which have a
long variable arm, has been revealed. The distinctions, revealed in the
tertiary structures of tRNASer, tRNATyr and tRNALeu, using the methods of
X-ray structure analysis and chemical modification, allow to understand the
importance of their role in the identification and discrimination by
homologous aaRSs.
The aim of one my project is studying of the molecular mechanisms of editing
during aminoacyl-tRNA synthesis for two aminoacyl-tRNA synthetases from two
different classes: leucyl- (a class I) and prolyl-tRNA synthetases (a class
II).
The differences between human and prokaryotic synthetases are using for
development of novel classes of antibiotics against Enterococcus faecalis
and Mycobacterium tuberculosis.
Number of publications: 186.
Telephone: +380 44 5265589.
Telephone home: +380 44 5692106.
Fax: +380 44 5260759.
E-mail: mtukalo@imbg.org.ua.
Selected publications :
english version