D-Alanyl-D-alanine terminus of bacterial peptidoglycan precursor (None commonly used.)

The D-Ala-D-Ala terminus is a short dipeptide at the end of peptidoglycan precursor pentapeptides in most bacterial species, especially Gram-positive. This motif is generated in the cytoplasm by D-Ala-D-Ala ligase and incorporated in lipid II, which is then used for cell wall assembly by transglycosylases and transpeptidases. Vancomycin and related glycopeptides specifically recognize and bind this motif by hydrogen bonding, blocking cell wall cross-linking and resulting in bacterial death. Many bacteria have evolved resistance mechanisms by substituting D-Ala-D-Ala with D-Ala-D-Lac or D-Ala-D-Ser, greatly reducing glycopeptide binding. As a non-protein, non-enzyme motif, the D-Ala-D-Ala terminus is best classified as a chemical target structure involved in bacterial cell wall assembly, not a classical receptor or enzyme. Its direct involvement in antibiotic resistance makes it an important target in infectious diseases, especially the treatment of multidrug-resistant organisms.

Other names

D-Ala-D-AlaD-Alanyl-D-alanine terminusPeptidoglycan D-Ala-D-AlaLipid II D-Ala-D-AlaPeptidoglycan precursor pentapeptide terminus

Glycopeptides (vancomycin, teicoplanin) bind to the D-Ala-D-Ala terminus, inhibiting transpeptidation and transglycosylation by physically blocking enzymes responsible for cross-linking peptidoglycan chains, thus preventing bacterial cell wall formation and causing cell death. D-cycloserine inhibits D-Ala-D-Ala ligase needed for terminus formation.