European Journal of Clinical Microbiology and Infectious Diseases

, Volume 8, Issue 11, pp 943–950

Structure, biochemistry and mechanism of action of glycopeptide antibiotics

Authors

  • P. E. Reynolds
    • Department of BiochemistryUniversity of Cambridge
Review

DOI: 10.1007/BF01967563

Cite this article as:
Reynolds, P.E. Eur. J. Clin. Microbiol. Infect. Dis. (1989) 8: 943. doi:10.1007/BF01967563
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Abstract

Glycopeptide antibiotics, including vancomycin and teicoplanin, are large, rigid molecules that inhibit a late stage in bacterial cell wall peptidoglycan synthesis. The three-dimensional structure contains a cleft into which peptides of highly specific configuration (L-aa-D-aa-D-aa) can fit: such sequences are found only in bacterial cell walls, hence glycopeptides are selectively toxic. Glycopeptides interact with peptides of this conformation by hydrogen bonding, forming stable complexes. As a result of binding to L-aa-D-Ala-D-Ala groups in wall intermediates, glycopeptides inhibit, apparently by steric hindrance, the formation of the backbone glycan chains (catalysed by peptidoglycan polymerase) from the simple wall subunits as they are extruded through the cytoplasmic membrane. The subsequent transpeptidation reaction that imparts rigidity to the cell wall is also thus inhibited. This unique mechanism of action, involving binding of the bulky inhibitor to the substrate outside the membrane so that the active sites of two enzymes cannot align themselves correctly, renders the acquisition of resistance to the glycopeptide antibiotics more difficult than that to the majority of the other antibiotic groups.

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© Friedr. Vieweg & Sohn Verlagsgesellschaft MbH 1989