D-alanyl-D-alanine terminus of peptidoglycan precursor unit

The D-alanyl-D-alanine terminus of peptidoglycan precursor units is a highly conserved dipeptide that constitutes the terminal amino acids of the peptide sidechain in the nascent peptidoglycan subunits (often on a MurNAc sugar via a pentapeptide stem). This terminus serves as the primary substrate for bacterial transpeptidase enzymes (penicillin-binding proteins) that catalyze the crosslinking of peptidoglycan strands, an essential step in bacterial cell wall biosynthesis[2][3][4][5]. Glycopeptide antibiotics such as vancomycin target this terminus by forming stable non-covalent interactions, thereby preventing proper cell wall assembly, which is lethal to bacteria. Bacterial resistance often develops via substitution of the D-alanyl-D-alanine terminus with alternative structures such as D-alanyl-D-lactate, which reduces antibiotic binding and confers resistance[1][8]. This target is critical for the mechanism of several clinically important antibiotics and is a major determinant in the efficacy and resistance profile of these agents.

Other names

D-Ala-D-Ala terminusD-ala-D-ala moietyD-alanyl-D-alanine endterminal D-alanyl-D-alanineD-alanyl-D-alanine of peptidoglycan precursor

Glycopeptide antibiotics (e.g., vancomycin) bind to the D-alanyl-D-alanine terminus, sterically blocking the action of transpeptidase and transglycosylase enzymes, thus inhibiting crosslinking and elongation of the peptidoglycan, leading to bactericidal cell death[1][8].