Peptidoglycan D-alanyl-D-alanine terminus (D-Ala-D-Ala terminus)

The **peptidoglycan D-alanyl-D-alanine terminus** is a dipeptidic motif forming the C-terminal region of peptidoglycan precursor peptide stems in bacterial cell wall biosynthesis. It serves as the substrate for transpeptidase enzymes (penicillin-binding proteins) that cross-link peptidoglycan chains, a process critical for bacterial cell wall strength and integrity[1][3][9][10]. Many clinically important antibiotics, including glycopeptides such as vancomycin and β-lactam agents, exert their effects by targeting this terminus or its functional site, thereby inhibiting cell wall assembly and leading to bacterial cell death[4][5][10]. Resistance can occur when bacteria alter this target, as seen with vancomycin-resistant enterococci replacing D-Ala-D-Ala with D-Ala-D-Lac or D-Ala-D-Ser, reducing antibiotic binding affinity[5][7][9]. This structure is absent in human cells, conferring high bacterial specificity to interacting drugs.

Other names

D-alanyl-D-alanine terminusD-Ala-D-Ala sitePeptidoglycan precursor C-terminal dipeptide

Inhibition of cell wall biosynthesis via binding to the D-Ala-D-Ala terminus of peptidoglycan precursors, preventing cross-linking (glycopeptides, e.g. vancomycin) Competitive inhibition of transpeptidase enzymes by β-lactam antibiotics due to structural mimicry of the D-Ala-D-Ala moiety, thus interfering with cross-linking