The nisin-lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics.Hsu, S.T., Breukink, E., Tischenko, E., Lutters, M.A., de Kruijff, B., Kaptein, R., Bonvin, A.M., van Nuland, N.A.
(2004) Nat. Struct. Mol. Biol. 11: 963-967
- PubMed: 15361862
- DOI: 10.1038/nsmb830
- Also Cited By: 1W9N
- PubMed Abstract:
- Mapping the Targeted Membrane Pore Formation Mechanism by Solution NMR: The Nisin Z and Lipid II Interaction in Sds Micelles
Hsu, S.-T.D.,Breukink, E.,de Kruijff, B.,Kaptein, R.,Bonvin, A.M.J.J.,van Nuland, N.A.J.
(2002) Biochemistry 41: 7670
- Use of the Cell Wall Precursor Lipid II by a Pore- Forming Peptide Antibiotic
Breukink, E.,Wiedemann, I.,van Kraaij, C.,Kuipers, O.P.,Sahl, H.G.,de Kruijff, B.
(1999) Science 286: 2361
- Refinement of Protein Structures in Explicit Solvent
Linge, J.,Williams, M.A.,Spronk, C.A.E.M.,Bonvin, A.M.J.J.,Nilges, M.
(2003) Proteins: Struct.,Funct., Genet. 50: 496
- Haddock: A Protein-Protein Docking Approach Based on Biochemical or Biophysical Information
Dominguez, C.,Boelens, R.,Bonvin, A.M.J.J.
(2003) J.Am.Chem.Soc. 125: 1731
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 uni ...
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.
Department of NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584CH Utrecht, The Netherlands.