Vancomycin pentapeptide binding

Figure 7 Peptidoglycan and vancomycin action. Vancomycin interacts with the terminal D-alanyl-D alanine residues of the peptidoglycan precursor, shown as the membranc associated lipid-disaccharide pentapeptide. Binding of vancomycin prevents both transglycosylation to the sugar backbone and transpeptidation. (Based on data reviewed in Ref. 39.)...

The peptidoglycan layer confers mechanical stability to the cell wall of the bacteria. An important intermediate of the peptidoglycan biosynthesis is the GlcNAc- MurNAc-L-Ala-D-y-Gln-L-Lys-D-Ala-D-Ala peptide (muramyl-pentapeptide), which is in its lipid-carrrier bound form transglycosylated to a linear polysaccharide. The linear polysaccharide is then cross-linked to peptidoglycan by transpeptidation reactions. Perkins observed that vancomycin binds to the Lys-D-Ala-D-Ala peptide motif of bacterial cell wall intermediates. This observation was later investigated on a mole-cular level by NMR and by x-ray crystallographic studies. ... 

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