D-alanyl-D-alanine motif of peptidoglycan precursor

The D-alanyl-D-alanine motif of peptidoglycan precursor is a highly conserved dipeptide sequence at the terminus of the peptide stem of peptidoglycan precursors in most Gram-positive and Gram-negative bacteria[6][3][8]. This motif is essential for the cross-linking reactions catalyzed by transpeptidases (penicillin-binding proteins), which confer strength and rigidity to the bacterial cell wall[6][3]. Antibiotics such as vancomycin target this motif by binding directly, thereby blocking further cell wall synthesis and resulting in bacterial cell death[1][5][7]. Changes in this motif (to D-Ala-D-Lac or D-Ala-D-Ser) are a key mechanism of resistance to glycopeptide antibiotics in some pathogenic bacteria, as these modifications dramatically decrease antibiotic binding affinity[1][5]. The D-Ala-D-Ala motif is not present in mammalian cells, making it an excellent, highly selective antibacterial target[7].

Other names

D-Ala-D-Ala dipeptideD-alanyl-D-alanineD-Ala-D-Ala motif

Glycopeptide antibiotics (e.g., vancomycin) bind the D-Ala-D-Ala motif, blocking transglycosylation and transpeptidation, and thus preventing cell wall synthesis[1][5][7]. β-lactams mimic the D-Ala-D-Ala motif and irreversibly inhibit transpeptidases (penicillin-binding proteins), preventing cross-linking of the cell wall[7].