D-alanyl-D-alanine terminus of Lipid II

The D-alanyl-D-alanine terminus refers to the C-terminal dipeptide of the pentapeptide stem on the peptidoglycan precursor Lipid II[1][8]. Lipid II is a crucial molecule in bacterial cell wall synthesis, serving as the primary building block for peptidoglycan polymerization and cross-linking[5][6]. The D-Ala-D-Ala motif is highly solvent-accessible and flexible, functioning as the recognition site for bacterial transpeptidase enzymes and as the primary binding site for many antibiotics, notably vancomycin and related glycopeptides[1][2]. Disruption of this motif by drugs effectively halts cell wall assembly, thereby inhibiting bacterial growth and survival[2][8]. Bacterial resistance mechanisms (e.g., D-Ala-D-Lac replacement) exploit this site to evade antibiotic binding[2][8]. This motif does not represent a conventional receptor, enzyme, or transporter, but is nonetheless a validated and essential therapeutic target within bacterial physiology.

Other names

D-Ala-D-Ala terminusD-alanyl-D-alanine moietypeptidoglycan C-terminal dipeptide

Drug binding to D-Ala-D-Ala motif inhibits transpeptidase-mediated crosslinking of peptidoglycan, blocking cell wall synthesis and causing bacteriolysis