D-alanyl-D-alanine moiety of peptidoglycan precursor (Lipid II)

The **D-alanyl-D-alanine moiety of peptidoglycan precursor (Lipid II)** is a short terminal dipeptide on the peptidoglycan pentapeptide stem, typically found as the final two amino acids (positions 4 and 5) on the stem peptide attached to the N-acetylmuramic acid of Lipid II in bacterial cell wall synthesis[1][2][5][7]. This functional group is the canonical binding site for glycopeptide antibiotics such as vancomycin, which interact with the D-Ala-D-Ala dipeptide via a series of hydrogen bonds, blocking the access of penicillin-binding proteins (transglycosylases and transpeptidases) and inhibiting cell wall cross-linking[3][8]. The presence of D-Ala-D-Ala is therefore essential for bacterial viability and the primary target of several important antibacterial drugs, but its structure is frequently modified in resistant pathogens (e.g., replaced by D-Ala-D-Lac or D-Ala-D-Ser), which abolishes high-affinity drug binding and confers clinically relevant antibiotic resistance[1][3][4]. The D-Ala-D-Ala moiety is not a protein, receptor, or enzyme in the classical sense but rather a structurally conserved motif critical to bacterial cell wall assembly and a validated drug target in clinical therapeutics[2][3][4].

Other names

D-Ala-D-Ala terminus of peptidoglycanD-Ala-D-Ala endD-alanyl-D-alanine moietyLipid II terminal D-Ala-D-Alapeptidoglycan pentapeptide D-Ala-D-Alavancomycin binding site

Direct binding of glycopeptide antibiotics (e.g., vancomycin) to the D-Ala-D-Ala terminus inhibits transglycosylation and transpeptidation, blocking peptidoglycan cross-linking and cell wall synthesis, leading to bacterial cell death[1][2][3][8].