LAUSR

Streptococcus pneumoniae is the most frequent cause of fatal bacterial pneumonia infection worldwide. Due to the spreading of antibiotic-resistant pathogens, it is important to search for new therapeutic and prevention strategies against bacterial infections. It is believed that the search for effective inhibitors of bacterial and pathogenic metallopeptidases could be one of the innovative strategies for the design of new antibiotics. Most of them contain zinc in the metal-binding site of the protein, which is a critical component for the biological activity of the enzyme. The main goal of this work is to determine the specificity of the interactions between the binding domain of the metallopeptidase from S. pneumoniae, and Zn(II). Considering the observed inhibitory role of copper towards the metallopeptidases, the next step is to analyze the formation of complexes with Cu(II) and Ni(II). The thermodynamic properties of Zn(II), Cu(II), and Ni(II) complexes were examined by potentiometry, NMR, MS, UV-Vis, CD, and EPR. The results show a similar coordination pattern, HExxHxxxxxH, for all three studied metals below pH 7. Moreover, the primary binding sites were established as the N-terminus in all cases. However, at a pH value of 7.4, the coordination and geometry of the formed complexes differ. The comparison of the stability of the formed complexes reveals that both Cu(II) and Ni(II) are able to displace Zn(II) from its binding site in the whole studied pH range. It opens a discussion on the catalytic zinc ion displacement possibilities by other divalent metal ions and the importance of this process in enzymatic inhibition.