Terminal D-alanyl-D-alanine of peptidoglycan precursor

The **terminal D-alanyl-D-alanine** of peptidoglycan precursor is a specific dipeptide motif located at the end of the pentapeptide stem of the nascent peptidoglycan subunits in most bacteria[3][6][7][2]. These peptidoglycan precursors are critical intermediates in bacterial cell wall biosynthesis: they are transported to the outer face of the cytoplasmic membrane, where they are polymerized and cross-linked to form the rigid peptidoglycan mesh that protects bacterial cells from osmotic pressure and environmental stress[1][6][2]. The D-alanyl-D-alanine motif is the recognition site for both cell wall-assembling enzymes (penicillin-binding proteins, transpeptidases) and for glycopeptide antibiotics such as vancomycin, which bind tightly to it and thereby prevent proper formation and cross-linking of the peptidoglycan, leading to bacterial death[6][2]. Resistance to vancomycin is associated with mutations in bacteria that replace this motif, most commonly with D-alanyl-D-lactate, thus reducing antibiotic affinity[6]. This motif is not a protein or receptor, but a chemically well-defined bacterium-specific peptide structure, and is a validated therapeutic target for several clinically-important antibiotics.

Other names

D-Ala-D-Ala motifTerminal D-alanyl-D-alaninePeptidoglycan D-Ala-D-AlaD-alanyl-D-alanine terminus

Glycopeptide antibiotics (e.g., vancomycin) bind to the terminal D-alanyl-D-alanine motif of peptidoglycan precursors, inhibiting transglycosylation and transpeptidation required for cell wall cross-linking, and thereby blocking bacterial cell wall synthesis[6][3][2].