Biochemistry

A Lipid II Sandwich

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Science  01 Aug 2003:
Vol. 301, Issue 5633, pp. 567
DOI: 10.1126/science.301.5633.567d

In their endless struggle to survive, microorganisms have developed a versatile armory of molecular weaponry. Many of these compounds act by inhibiting essential enzymatic reactions, such as ribosomal protein synthesis, but others, of which the most widely useful and used is vancomycin, bind to building blocks of the peptidoglycan, the cross-linked foundation of the bacterial cell wall. The emergence of bacteria resistant to vancomycin has motivated a search for new antibiotics; one such candidate is ramoplanin, a cyclic peptide made of 17 amino acids and 2 saccharides. Hu et al. have shown by enzyme kinetics that it binds to lipid II, which carries a pentapeptide-disaccharide intermediate from the cytoplasm to the cell wall assembly site, and that it does so with a 2:1 stoichiometry of ramoplanin: lipid II. One of the critical interactions involves the distal amino group of ornithine-10, which sits at the mouth of a proposed binding cleft for lipid II. — GJC

J. Am. Chem. Soc. 125, 8736 (2003).

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