The peptidoglycan is an essential component of the cell wall of Gram-positive and Gram-negative bacteria, and its absence or deficiency can lead to cell death making it an excellent target for the development of new antibiotics. However, due to the increasing antibiotic resistence by many microorganisms, the search for new molecular and antimicrobial targets has resurfaced, directing the studies to other steps and enzymes involved in peptidoglycan biosynthesis. The initial steps of this biosynthesis are performed in the cytoplasm by Mur enzymes, forming UDP-MurNAc-pentapeptide. Many inhibitors have been characterized in vitro for these enzymes. Although lack of evidence of its functionality in vivo raises the hypothesis that these inhibitors do not have access to the active site of the enzymes in the bacterial cytoplasm due to the possible formation of a megaprotein complex whose structure would block the catalytic sites. Further studies reinforce this hypothesis, demonstrating that Mur enzymes are capable of forming oligomers and of interacting with other Mur enzymes, forming binary complexes. Thus, this Master project aims to continue the characterization of Mur enzymes from Streptococcus pneumoniae, especially the direct interactions, crystallization and structure resolution of the binary complex between MurC and MurD (ATP-dependent Mur ligases), and, if possible, MurG. The results will provide more information for a better understanding of the bacterial peptidoglycan formation process, which may be useful for the eventual development of new antibiotics targeting this pathway.
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