Lipid II D-alanyl-D-alanine terminus (Lipid II D-Ala-D-Ala)

Lipid II is a vital precursor in the synthesis of the bacterial cell wall, acting as a shuttle that transports peptidoglycan subunits across the cell membrane (Bugg et al., 2011). The D-alanyl-D-alanine (D-Ala-D-Ala) terminus of the Lipid II pentapeptide is the specific molecular target for glycopeptide antibiotics like vancomycin (Kahne et al., 2005). These antibiotics bind to the D-Ala-D-Ala motif through a network of hydrogen bonds, creating a physical barrier that prevents the incorporation of the precursor into the growing peptidoglycan chain (StatPearls, 2023). This blockage inhibits both transglycosylation and transpeptidation, the final steps of cell wall assembly, leading to a weakened cell wall and subsequent bacterial death via osmotic lysis (PubMed, 2022). Because the D-Ala-D-Ala structure is absent in eukaryotic cells, it provides a high degree of selective toxicity for treating Gram-positive bacterial infections. However, clinical utility is increasingly threatened by the emergence of resistant strains that modify the terminus to D-alanyl-D-lactate or D-alanyl-D-serine, significantly reducing antibiotic binding affinity (Courvalin, 2006).

Other names

D-alanyl-D-alanine terminus of Lipid IIPeptidoglycan precursor D-Ala-D-AlaLipid II pentapeptide terminusD-Ala-D-Ala

Inhibition of bacterial cell wall synthesis by binding to the D-alanyl-D-alanine terminus of the peptidoglycan precursor Lipid II, thereby sterically hindering the transglycosylation and transpeptidation reactions necessary for peptidoglycan polymerization and cross-linking (Kahne et al., 2005; StatPearls, 2023).