Division of Biochemistry

Within several projects at the Division of Biochemistry, we investigate the structure, function and interactions of proteins and nucleic acids involved in the translation of the genetic message. Particular emphasis is placed on aminoacyl-tRNA synthetases, enzymes that catalyze the esterification of transfer RNA with the corresponding amino acids. Enzymes and other proteins are produced using genetic engineering methods, in their native or engineered forms. Enzymatic mechanisms are analyzed through kinetic parameters of biochemical reactions, determination of substrate-binding constants, and examination of the effects of different inhibitors. The biological relevance of introduced changes is additionally verified in vivo using genetic approaches. One of the recent research directions is the discovery of antibiotics targeting bacterial aminoacyl-tRNA synthetases. In addition, using proteomics approaches, we systematically investigate changes in expression levels and post-translational modifications of proteins under different cell growth conditions. Besides aminoacyl-tRNA synthetases, enzymes from the α/β-hydrolase family are also studied, with the aim of polymer degradation, with the current focus on polyesters. For this purpose, enzyme engineering methods are applied to improve enzyme properties, including solubility, increased melting temperature (Tm), and the introduction of new enzymatic activities. In collaboration with crystallographers, three-dimensional structures of the studied enzymes and their complexes with small molecules and macromolecules are determined and analyzed. Furthermore, computational force-field-based methods, such as molecular dynamics simulations and molecular docking, are used to study structural and dynamic properties of biological macromolecules.