D-alanyl-D-alanine terminus of peptidoglycan

The **D-alanyl-D-alanine terminus of peptidoglycan** is a structural dipeptide motif found at the end of the pentapeptide side chains within the peptidoglycan of bacterial cell walls[1][4][6]. This terminal moiety is critical for the cross-linking of glycan chains during cell wall synthesis, a reaction catalyzed by transpeptidase enzymes[6]. The D-alanyl-D-alanine motif is specifically recognized and bound by several glycopeptide antibiotics, including vancomycin, which inhibits cell wall biosynthesis by blocking the action of transpeptidases, resulting in compromised cell wall integrity and eventual bacterial lysis[1]. Drugs targeting this terminus exploit its absence in human cells, providing selective antibacterial activity[1]. However, bacterial resistance can occur if the motif is replaced by D-alanyl-D-lactate, as seen in vancomycin-resistant enterococci[1]. This target is not a protein, transporter, or receptor but rather a specific structural motif essential for the viability of many bacteria.

Other names

D-Ala-D-Ala terminusD-alanyl-D-alanine dipeptide terminusD-alanyl-D-alanine motifD-alanyl-D-alanine end

Inhibition of transpeptidase-mediated cross-linking of peptidoglycan by drug binding to D-alanyl-D-alanine terminus Prevention of peptidoglycan polymerization, leading to cell wall weakening and bacterial lysis