Peptidoglycan precursors containing D-alanyl-D-alanine (D-Ala-D-Ala)

Peptidoglycan precursors containing the D-alanyl-D-alanine (D-Ala-D-Ala) dipeptide are essential building blocks in the assembly of the bacterial cell wall, particularly in Gram-positive bacteria (Nature Reviews Microbiology, 2008). These precursors, including the membrane-anchored Lipid II, are synthesized in the cytoplasm and translocated to the outer surface of the cytoplasmic membrane. The D-Ala-D-Ala terminus acts as a critical recognition site for penicillin-binding proteins (PBPs), which facilitate the cross-linking of glycan strands to provide mechanical strength to the cell wall (PubMed, 2019). Glycopeptide antibiotics, such as vancomycin and teicoplanin, target this specific molecular motif by forming a complex via five hydrogen bonds (StatPearls, 2023). This interaction sterically blocks the enzymes responsible for peptidoglycan polymerization and cross-linking, leading to cell wall instability and osmotic lysis. Clinical resistance often arises through the metabolic reprogramming of these precursors to D-alanyl-D-lactate or D-alanyl-D-serine, which prevents antibiotic binding while maintaining cell wall function (Journal of Biological Chemistry, 2014).

Other names

D-alanyl-D-alanine terminusLipid IIUDP-N-acetylmuramyl-pentapeptidePeptidoglycan pentapeptide side chainD-Ala-D-Ala motif

Binding to the D-alanyl-D-alanine C-terminus of peptidoglycan precursors to sterically inhibit transglycosylation and transpeptidation during cell wall synthesis (StatPearls, 2023).