The nisin-lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics.

TitleThe nisin-lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics.
Publication TypeJournal Article
Year of Publication2004
AuthorsHsu, S-T. D., E. Breukink, E. Tischenko, M. A. G. Lutters, B. de Kruijff, R. Kaptein, A. M. J. J. Bonvin, and N. A. J. van Nuland
JournalNat Struct Mol Biol
Volume11
Issue10
Pagination963-7
Date Published2004 Oct
ISSN1545-9993
KeywordsAnti-Bacterial Agents, Diphosphates, Lipid Metabolism, Nisin
Abstract

The emerging antibiotics-resistance problem has underlined the urgent need for novel antimicrobial agents. Lantibiotics (lanthionine-containing antibiotics) are promising candidates to alleviate this problem. Nisin, a member of this family, has a unique pore-forming activity against bacteria. It binds to lipid II, the essential precursor of cell wall synthesis. As a result, the membrane permeabilization activity of nisin is increased by three orders of magnitude. Here we report the solution structure of the complex of nisin and lipid II. The structure shows a novel lipid II-binding motif in which the pyrophosphate moiety of lipid II is primarily coordinated by the N-terminal backbone amides of nisin via intermolecular hydrogen bonds. This cage structure provides a rationale for the conservation of the lanthionine rings among several lipid II-binding lantibiotics. The structure of the pyrophosphate cage offers a template for structure-based design of novel antibiotics.

DOI10.1038/nsmb830
Alternate JournalNat. Struct. Mol. Biol.
PubMed ID15361862