D-alanyl-D-alanine terminus in peptidoglycan precursor (D-Ala-D-Ala terminus)

The **D-alanyl-D-alanine terminus in peptidoglycan precursor** is a chemical motif representing the C-terminal end of the peptide stem in the peptidoglycan precursors of most bacterial cell walls. This dipeptide, added by the enzyme D-alanine-D-alanine ligase, is crucial for the proper cross-linking of peptidoglycan layers in both Gram-positive and Gram-negative bacteria, providing rigidity and maintaining cell shape. During cell wall synthesis, the D-Ala-D-Ala end serves as the specific binding site for glycopeptide antibiotics such as vancomycin, which form a stable complex with this motif and block further extension and cross-linking of the cell wall—ultimately causing bacterial death[1][2][3][4][5][6][7]. The D-Ala-D-Ala motif is also mimicked by β-lactam antibiotics to competitively inhibit cell wall transpeptidation. Bacterial resistance, notably vancomycin resistance, can arise by altering this terminus (e.g., replacing D-Ala-D-Ala with D-Ala-D-Lac), greatly reducing antibiotic binding affinity and efficacy[1]. This structure is unique to bacteria and absent in mammalian cells, making it an excellent, selective antibacterial drug target.

Other names

D-alanine-D-alanine terminusD-Ala-D-AlaD-Ala-D-Ala dipeptideD-Ala-D-Ala endpeptidoglycan D-Ala-D-Alapeptidoglycan pentapeptide terminus

Glycopeptide antibiotics (e.g., vancomycin) bind the D-Ala-D-Ala terminus, blocking peptidoglycan cross-linking and thus inhibiting bacterial cell wall synthesis, leading to cell death[1]. β-lactam antibiotics mimic the D-Ala-D-Ala structure, competitively inhibiting transpeptidases (penicillin-binding proteins), and preventing peptidoglycan cross-linking[5].