Solution NMR Studies of LPRDA Peptide: an Oligopeptide Inhibitor of Staphylococcus aureus Sortase A

Abstract

Sortases are Gram-positive bacterial extracellular transpeptidases involved in the attachment of surface proteins to the cell wall. The mechanism of action of Staphylococcus aureus Sortase A (SrtA) is based on specific recognition of the LPXTG motive at the C-terminus of the surface protein, cleavage of this site between threonine and glycine residues, subsequent transfer of the N-terminal transmembrane domain to the amino group of the pentaglycine linker and thus anchoring of proteins with this motive on the cell surface. As SrtA is involved in both early and late stages of bacterial infection because it attaches adhesins and immune evasion proteins to the cell wall, this enzyme is a good target for combating bacterial infections. The oligopeptide LPRDA was recently found to be an effective inhibitor of the enzymatic activity of SrtA through competitive binding to its active site. By NMR spectroscopy we solved the solution structure of the LPRDA peptide and showed the presence of several conformers in solution. The obtained data are the basis for further studies of the structure and function of peptidomimetics based on LPRDA oligopeptide.