Peptidoglycan precursor D-alanyl-D-alanine (D-Ala-D-Ala) terminus on lipid II (D-Ala-D-Ala)

The D-alanyl-D-alanine (D-Ala-D-Ala) terminus of the peptidoglycan precursor Lipid II is a fundamental structural component in the assembly of the bacterial cell wall, particularly in Gram-positive species (Nature Reviews Microbiology, 2008). Lipid II acts as a shuttle, transporting the building blocks of the peptidoglycan layer across the bacterial cell membrane. The terminal D-Ala-D-Ala dipeptide of the pentapeptide chain is the specific molecular target for glycopeptide antibiotics like vancomycin. When these drugs bind to the D-Ala-D-Ala motif, they create a steric block that prevents the enzymes transglycosylase and transpeptidase from incorporating the precursor into the growing peptidoglycan matrix (PubMed, PMID: 11586204). This inhibition halts cell wall synthesis, leading to bacterial lysis and death. Clinical resistance to these drugs often involves the enzymatic modification of the D-Ala-D-Ala terminus to D-Ala-D-Lac or D-Ala-D-Ser, which prevents antibiotic binding (StatPearls, 2023).

Other names

D-alanyl-D-alanineLipid II D-Ala-D-Ala terminusPeptidoglycan pentapeptide terminusD-Ala-D-Ala dipeptide

Glycopeptide antibiotics bind to the D-Ala-D-Ala terminus of the peptidoglycan precursor Lipid II via five hydrogen bonds, sterically inhibiting the transglycosylation and transpeptidation reactions required for cell wall synthesis (StatPearls, 2023).