D-alanyl-D-alanine dipeptide terminus of peptidoglycan precursor (D-Ala-D-Ala)

The **D-alanyl-D-alanine dipeptide terminus of peptidoglycan precursor** is a highly conserved C-terminal feature of the pentapeptide stem subunit in the peptidoglycan precursors that form the bacterial cell wall[1][2][3][4][7]. It is generated by the action of D-Ala-D-Ala ligase and incorporated into the growing peptidoglycan chain, serving as the substrate for transpeptidases and transglycosylases involved in crosslinking cell wall structures[2][7][9]. The D-Ala-D-Ala motif is selectively recognized and bound by glycopeptide antibiotics such as vancomycin, which inhibits cell wall synthesis and exerts bactericidal activity, making it a key therapeutic target for treating infections caused by Gram-positive bacteria[1][2][5][7]. Alteration of this motif (e.g., to D-Ala-D-Lac) underlies clinically significant resistance mechanisms[2][5]. This terminus is not a protein or classical receptor/enzyme but is instead a structural moiety critical for bacterial viability and the specific molecular target of several clinically important antimicrobial classes.

Other names

D-Ala-D-Ala terminusD-alanyl-D-alaninepeptidoglycan dipeptide terminusbacterial peptidoglycan precursor terminus

Glycopeptide antibiotics bind the D-Ala-D-Ala terminus, blocking access of transpeptidases and transglycosylases, thus **inhibiting cell wall cross-linking and extension**, leading to bacterial cell death[1][2][5][7] β-lactam antibiotics act as structural mimics of the D-Ala-D-Ala motif, inhibiting transpeptidase enzymes via **suicide inhibition** in a competitive manner[7] D-cycloserine inhibits synthesis of D-Ala-D-Ala by blocking the actions of alanine racemase and D-Ala-D-Ala ligase[10]