D-alanyl-D-alanine terminus of Lipid II (D-Ala-D-Ala) (D-Ala-D-Ala)

The D-alanyl-D-alanine (D-Ala-D-Ala) terminus of the Lipid II peptidoglycan precursor is a critical structural motif in the biosynthesis of the bacterial cell wall (Source: PubChem CID 16219615). Lipid II is a membrane-anchored intermediate that transports peptidoglycan subunits across the cytoplasmic membrane to the site of cell wall assembly (Source: Nature Reviews Microbiology, 2008). The D-Ala-D-Ala dipeptide at the end of the pentapeptide chain serves as the substrate for transpeptidase enzymes, also known as penicillin-binding proteins, which catalyze the cross-linking of the peptidoglycan layer (Source: PMC2823315). This cross-linking provides essential structural integrity and osmotic protection to the bacterium. This specific terminus is the primary molecular target for glycopeptide antibiotics, including vancomycin and teicoplanin (Source: StatPearls, NBK459358). These drugs bind to the D-Ala-D-Ala motif through a network of hydrogen bonds, effectively capping the precursor and sterically hindering the transglycosylation and transpeptidation reactions required for cell wall polymerization. Consequently, the bacterial cell wall cannot be properly formed, leading to cell lysis and death. Clinical resistance often arises when bacteria modify this target to D-alanyl-D-lactate (D-Ala-D-Lac), which drastically reduces antibiotic binding affinity (Source: PubMed, 11544343).

Other names

D-alanyl-D-alanineLipid II pentapeptide terminusPeptidoglycan precursor terminusD-Ala-D-Ala dipeptide

Binding to the D-Ala-D-Ala terminus of the peptidoglycan precursor Lipid II, thereby sterically inhibiting the transglycosylation and transpeptidation steps of cell wall synthesis (Source: StatPearls, NBK459358).