D-Alanyl-D-alanine terminus of cell wall peptidoglycan

The D-Alanyl-D-alanine terminus of cell wall peptidoglycan is a short peptide sequence (D-Ala-D-Ala) found at the end of the stem peptides within nascent bacterial peptidoglycan precursors, especially abundant in Gram-positive bacteria. It is critical for the final cross-linking (transpeptidation) reactions that provide bacterial cell wall rigidity and structural integrity[1][3][7]. This motif is the direct binding site for glycopeptide antibiotics such as vancomycin, which block the cross-linking of new cell wall subunits by capping this dipeptide and thereby halting cell wall biosynthesis, leading to bacteriolysis. Resistance can develop by alteration of this terminus, such as replacing the terminal D-Ala with D-lactate (D-Ala-D-Lac), reducing drug efficacy[6]. Targeting this motif underpins the mechanism of action for a major class of antibiotics used in serious infections due to Gram-positive bacteria.

Other names

D-Ala-D-Ala terminusD-Alanyl-D-alanine terminusPeptidoglycan D-Ala-D-Ala terminusTerminal D-alanine dipeptide

Inhibition of cell wall synthesis by sterically blocking transpeptidase (DD-transpeptidase) cross-linking at the D-Ala-D-Ala terminus Direct binding by glycopeptide antibiotics prevents addition of new peptidoglycan subunits