D-ALANYL-D-ALANINE LIGASES AND THE MOLECULAR MECHANISM OF VANCOMYCIN RESISTANCE

Bacteria resist hypotonic shock and cell lysis through the biosynthesis of peptidoglycan-containing cell walls. This rigid polymer consists of a repeating disaccharide unit of N-acetylglucosamine-( β l-4)-N-acetylmuramic acid to which a pentapeptide is linked through the muramyl lactyl ether carboxylate (Figure IB). The pentapeptide is composed of L-Ala- γ -D-Glu-(a dibasic amino acid: L-Lys or m-diaminopimelic acid)-D-Ala- D-Ala. Depending on the bacterial species and growth conditions, roughly 50-90 % of the free amines of the dibasic amino acid are recruited to form an amide crosslink with the penultimate D-Ala of another pentapeptide, either directly or through the intervention of a peptide linker such as Gly5. The net result of this transpeptidation reaction is the formation of a rigid framework which insulates the organism from external osmotic pressures. © 1992, American Chemical Society. All rights reserved.