MurNAcpentapeptide

MurNAc-pentapeptide refers to a fundamental building block of bacterial peptidoglycan. It is the disaccharide-peptide repeating unit in which N-acetylmuramic acid (MurNAc) is linked to a short peptide stem of five amino acids. The pentapeptide sequence varies among bacteria but commonly is L-Ala-D-Glu-m-DAP-D-Ala-D-Ala in many Gram-negative species, or L-Ala-D-Glu-L-Lys-D-Ala-D-Ala in many Gram-positive species. The third residue is often a meso-diaminopimelic acid (m-DAP) or lysine, and the terminal D-Ala-D-Ala dipeptide is the substrate for cross-linking reactions that strengthen the cell wall.

Structure and role in peptidoglycan synthesis

MurNAc provides the sugar backbone, while the attached pentapeptide serves as the donor for interpeptide cross-links between neighboring glycan chains. Cross-linking is performed by penicillin-binding proteins (PBPs) through transpeptidation, typically linking the fourth and fifth positions of one stem to the third residue of an adjacent stem. This cross-linking confers rigid, mesh-like strength to the cell wall and is essential for maintaining cellular integrity during growth and division.

Biosynthesis and integration

In the cytoplasm, enzymes (murA, murB, murC, murD, murE, murF) assemble UDP-MurNAc-pentapeptide. This intermediate is attached to a lipid carrier by MraY and then flipped across the membrane to form Lipid II, which is recycled into peptidoglycan by transglycosylases and transpeptidases. The MurNAc-pentapeptide composition influences cross-linking and wall architecture, and variations help determine antibiotic susceptibility.

Clinical relevance

MurNAc-pentapeptide and its incorporation into peptidoglycan are targets for antibiotics such as β-lactams (PBPs) and glycopeptides (D-Ala-D-Ala binding). Understanding its structure aids in deciphering mechanisms of resistance and the development of new antibacterial strategies.