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Department of Protein Engineering and Bioinformatics
Head: O. I.Kornelyuk, Dr.Sci.(Biol.), Professor
E-ma³le: kornelyuk@³mbg.org.ua
The Department Protein Engineering and Bioinformatics was founded in 2001, aimed at the development of protein Engineering and Bioinformatics and structural bioinformatics as the new fields of molecular biology. The major fundamental research of the Department is focused on the study of molecular mechanism of aminoacyl-tRNA synthetases (ARS) of higher eukaryotes and the functional role of protein dynamics in the process of protein-nucleic acid recognition. The methods of protein Engineering and Bioinformatics are being used, aimed at the design of new proteins with modified and unique properties. The design of proteins is carried out in order to study the structural and functional role of specific aminoacid residues, motives and protein domains. The Department has elaborated the gene Engineering and Bioinformatics technologies of the cloning and expression of eukaryotic proteins and their mutants. The structural and functional relations in a protein molecule were used as a basis for formulating the principles of protein structure modification. The addressed mutations in a protein structure are performed by the site-directed mutagenesis methods.
The primary structure of tyrosyl- tRNA synthetase (TyrRS) has been determined at the Department . The homology of non-catalytic C-terminal domain of synthetase with a new cytokine – endothelium and monocytactivating polypeptide II (EMAP II) has been revealed. In order to explore the functions of C-module, the bacterial expression and isolation of the cytokine-like C-terminal module TyrRS was carried out. In 1999 in collaboration with the Nottingham University (United Kingdom), the cytokine activity of isolated C-module as a novel non-canonical function of eukaryotic ARSes, was discovered . Also, the effect of synergism between the TyrRS C-module and another cytokine, a tumour necrosis factor a has been discovered. The site-directed mutagenesis of C-module surface residues in the region of oligomer interface made it possible to obtain a mutant protein which didn’t revealed a tendency of oligomerization.
Using the methods of protein Engineering and Bioinformatics, it has been shown for mammalian TyrRS that Lys146 residue plays a key functional role in the stabilization of transition state of the reaction of homologous tRNATyr aminoacylation.
The Department is elaborating the structural and dynamic model of RNA recognition by ARSes. The experimental investigations of the intramolecular dynamics of proteins are performed using the methods of fluorescent spectroscopy. Specific conformational alterations of enzymes, occurring in the process of substrate recognition, are being studied. The method of molecular dynamics simulation is also employed for the study of conformational mobility of TyrRS and separate domains.
For the last years, structural bioinformatics has been intensively developing as a novel research direction. The methods of computer analysis are widely employed in the process of modelling of the protein three-dimensional structure and macromolecular complexes, their dynamics and the recognition mechanism. The final objective of this research is the design of the selective modulators of proteins functional activities as potential novel drugs.
The protease of human immunodeficiency virus (HIV-1 protease) was used as a target protein for making antiviral drugs. The dynamics of HIV-1 protease in solution and the role that ions play in the stabilization of the active centre have been studied and specific conformational alterations of enzyme have been revealed. In order to understand the mechanism of HIV-1 protease resistance to inhibitors in the AIDS therapy, the molecular dynamics of several mutant forms of HIV-1 protease has been analysed .
The comparative analysis of the gene structure of cytoplasmic TyrRS has been performed in 29 eukaryotic organisms, which belong to different taxons and their exon – intron structure and the promoters composition have been predicted. The methods of microarray bioinformatics are widely used in the analysis of gene expression.
The first web-portal BioUA (http://www.bioua.org.ua) as bioinformatics resources of the IMBiG of the NASU has been established in order to facilitate the research in bioinformatics, genomics and structural biology.
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English version