The research of the Division of Biochemistry is focused on protein translation with the emphasis on aminoacyl-tRNA synthetases, the enzymes that catalyze the covalent coupling of cognate pairs of amino acids and tRNAs thus translating genetic information into the amino acid sequence. Erroneously synthesized proteins affect cell viability and are associated with aging and the development of neurodegenerative diseases. Using kinetic, biochemical, biophysical, genetic, proteomic and computational approaches, we investigate the mechanism, evolution and biological importance of both substrate specificity and editing of aminoacyl tRNA-synthetases that evolved under strong evolutionary pressure to keep a high level of translation fidelity.
Aminoacyl-tRNA synthetases, being house-keeping enzymes, are promising targets for natural antibiotics and the development of synthetic drugs. Using complementary biochemical, evolutionary and structural biology approaches, we investigate the main aspects of the mechanism of antibiotics action and development of antibiotic resistance as well as the interdependence of antibiotic resistance and the fidelity of translation.
Aminoacyl-tRNA synthetases are often involved in a variety of cellular processes not directly related to protein biosynthesis. We study their non-canonical functions in plant aminoacyl-tRNA synthetases which are generally less studied. We are also engaged in studying the non-canonical roles of bacterial aminoacyl-tRNA synthetases in complex cellular processes such as biofilm formation and sporulation.
Selected publications 2019/2020
1. Baranašić, J., Mihalak, A., Gruić-Sovulj, I., Bauer, N., Rokov-Plavec, J.: Expression of genes for selected plant aminoacyl-tRNA synthetases in the abiotic stress. Acta Botanica Croatica, DOI: 10.37427/botcro-2021-010.
2. Tawfik, D.S., Gruic-Sovulj, I. How evolution shapes enzyme selectivity – lessons from aminoacyl-tRNA synthetases and other amino acid utilizing enzymes FEBS Journal, 2020, 287(7), pp. 1284-1305
3. Zivkovic, I., Moschner, J., Koksch, B., Gruic-Sovulj, I. Mechanism of discrimination of isoleucyl-tRNA synthetase against nonproteinogenic α-aminobutyrate and its fluorinated analogues FEBS Journal, 2020, 287(4), pp. 800-813
4. Maršavelski, A., Sabljić, I., Sugimori, D., Kojić-Prodić, B. The substrate selectivity of the two homologous SGNH hydrolases from Streptomyces bacteria: Molecular dynamics and experimental study International Journal of Biological Macromolecules, 2020, 158, pp. 222-230
5. Palčić, A., Babić, S., Maršavelski, A., Galić M., Topić Popović, N., Strunjak Perović, I., Čož-Rakov R., Bronić, J., Valtchev, V. Nanosized zeolite beta - Determining the safety of usage by zebrafish Danio rerio embryos Microporous and Mesoporous Materials, 2020, 299, 110103
6. Bilus, M., Semanjski, M., Mocibob, M., Zivkovic, I., Cvetesic N., Tawfik D. S., Toth-Petroczy A., Macek, B., Gruic-Sovulj, I. On the Mechanism and Origin of Isoleucyl-tRNA Synthetase Editing against Norvaline Journal of Molecular Biology, 2019, 431(6), pp. 1284-1297
7. Kekez, M., Zanki, V., Kekez, I., Baranasic, J., Hodnik, V., Duchêne, A.-M., Anderluh, G., Gruic-Sovulj, I., Matković-Čalogović, D., Weygand-Durasevic, I., Rokov-Plavec J., Arabidopsis seryl-tRNA synthetase: the first crystal structure and novel protein interactor of plant aminoacyl-tRNA synthetase FEBS Journal, 2019, 286(3), pp. 536-554
8. Bauer, N., Škiljaica, A., Malenica, N., Razdorov, G., Klasić, M., Juranić, M., Močibob, M. Sprunck, S., Dresselhaus, T., Leljak Levanić, D. The MATH-BTB Protein TaMAB2 Accumulates in Ubiquitin-containing foci and Interacts with the translation initiation machinery in Arabidopsis frontiers in plant science, 2019, 10, 1469
9. Baumann, K., Kordić, L., Močibob, M., Šinko, G., Tomić, S. Synthesis and in vitro screening of novel heterocyclic β-D-gluco- And β-D-galactoconjugates as butyrylcholinesterase inhibitors Molecules, 2019, 24(15), 2833
10. Raos, M., Zunec, R., Mocibob, M., Gojceta, K., Lukic, M., Golubic Cepulic, B. Susceptible and protective HLA-DR and HLA-DQ alleles for Fy a alloimmunization in the Croatian population Transfusion, 2019, 59(3), pp. 1118-1124
2017-2021 Aminoacyl-tRNA synthetases as gatekeepers of the standard genetic code
Funding: Croatian Science Foundation (HrZZ)
Principal investigator: prof. dr. sc. Ita Gruić Sovulj
2019-2022 Investigation of substrate and editing specificity in tRNA synthetases and the mechanism of antibiotic action
Funding: Croatian Science Foundation and Swiss National Science Foundation (a bilateral Croatian-Swiss project)
Principal investigators: Professor Ita Gruić Sovulj and Professor Nenad Ban
Assistant Professor Morana Dulić, PhD: thermodynamic and kinetic approaches to aminoacyl-tRNA synthetases, editing, molecular evolution
Professor Ita Gruić Sovulj, Phd: substrate specificities, editing and evolution of aminoacyl-tRNA synthetases, antibiotic resistance, translation fidelity
Assistant Professor Aleksandra Maršavelski, PhD: modeling of biological macromolecules and their complexes
Assistant Professor Marko Močibob, PhD: noncanonical roles of aminoacyl-tRNA synthetases and their homologs, the impact of compromised translational fidelity on protein structure, stability and cell viability
Assistant Professor Jasmina Rokov Plavec, PhD: structure and function of plant aminoacyl-tRNA synthetases, the relationship between translation and environmental stress, protein interactions