Researchers from the Chemistry Department, Katarina Radman, Nikola Bregović and Branimir Bertoša, and a recent researcher from the Chemistry Department, Zoe Jelić Matošević, in collaboration with researchers from the Ruđer Bošković Institute (Ivo Crnolatac, Ivo Piantanida, Dalibor Merunka, Dijana Žilić, Ivana Leščić Ašler) and researcher from University of Porto (Pedro A. Fernandes) have published the scientific publication: Conformational change induced by binding of Mn2+ ions activates SloR transcription factor in Streptococcus mutans. The paper was published in the prestigious journal International Journal of Biological Macromolecules (IF = 7.7).
The published results were obtained through study of the allosteric mechanism by which one of the manganese metal sensors, specifically the transcription factor SloR, regulates manganese ion homeostasis in the bacterium Streptococcus mutans. Using computational methods, including molecular dynamics simulations and quantum mechanical calculations, changes in the structural and dynamic properties of the SloR protein upon binding of manganese ions were explored. Computational results were verified with experimental data obtained using circular dichroism (CD) spectroscopy, microcalorimetry (DSC, ITC), and electron paramagnetic resonance (EPR) spectroscopy. The synergy of computational and experimental results provided a comprehensive understanding of the allosteric mechanism, which begins with the binding of manganese ions to the binding sites of the SloR protein. The conclusion is that the presence of manganese ions causes a conformational change of the protein, primarily reflected in the orientation and flexibility of the DNA-binding domains, ultimately leading to an increased affinity of the SloR protein for DNA binding.
The published results were obtained as part of research conducted within the framework of the project "Manganese Metallosensors" (IP-2020-02-3446) funded by the Croatian Science Foundation, and represent the core of the doctoral thesis of Katarina Radman conducted under the supervision of Ivana Leščić Ašler and Branimir Bertoša.
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