D-alanyl–D-alanine terminus of peptidoglycan precursor (null)

The D-alanyl–D-alanine terminus of peptidoglycan precursor is a dipeptide motif located at the terminal end of the pentapeptide stem in nascent bacterial cell wall precursor molecules, specifically Lipid II. Its presence enables enzymes (penicillin-binding proteins, transpeptidases) to crosslink peptidoglycan strands, forming the structural scaffold of bacterial cell walls. Crucially, this motif is the binding site for glycopeptide antibiotics such as vancomycin, which recognize and sequester the D-Ala–D-Ala dipeptide, thereby inhibiting cell wall crosslinking and exerting bactericidal action. Bacteria can evade this lethal mechanism by replacing the D-Ala–D-Ala motif with D-Ala–D-Lac or D-Ala–D-Ser, drastically reducing antibiotic affinity and causing resistance. This motif is not a single protein or gene, but a chemically defined structure, and its presence or absence directly determines susceptibility to several last-line antibiotics.

Other names

D-Ala–D-AlaD-alanyl–D-alanine terminusPeptidoglycan D-Ala–D-Ala siteD-Ala-D-Ala motifPeptidoglycan precursor pentapeptide

Glycopeptide antibiotics (e.g., vancomycin) bind non-covalently to the D-Ala–D-Ala terminus, sterically hindering transpeptidase enzymes involved in crosslinking, thereby inhibiting cell wall synthesis and causing bacterial cell death. Resistance arises when the D-Ala–D-Ala motif is enzymatically replaced by D-Ala–D-Lac or D-Ala-D-Ser, resulting in loss of glycopeptide binding.