| Plectasin, a fungal defensin, targets the bacterial cell wall precursor Lipid II. | |
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MedLine Citation:
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PMID: 20508130 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Host defense peptides such as defensins are components of innate immunity and have retained antibiotic activity throughout evolution. Their activity is thought to be due to amphipathic structures, which enable binding and disruption of microbial cytoplasmic membranes. Contrary to this, we show that plectasin, a fungal defensin, acts by directly binding the bacterial cell-wall precursor Lipid II. A wide range of genetic and biochemical approaches identify cell-wall biosynthesis as the pathway targeted by plectasin. In vitro assays for cell-wall synthesis identified Lipid II as the specific cellular target. Consistently, binding studies confirmed the formation of an equimolar stoichiometric complex between Lipid II and plectasin. Furthermore, key residues in plectasin involved in complex formation were identified using nuclear magnetic resonance spectroscopy and computational modeling. |
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Authors:
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Tanja Schneider; Thomas Kruse; Reinhard Wimmer; Imke Wiedemann; Vera Sass; Ulrike Pag; Andrea Jansen; Allan K Nielsen; Per H Mygind; Dorotea S Ravent?s; S?ren Neve; Birthe Ravn; Alexandre M J J Bonvin; Leonardo De Maria; Anders S Andersen; Lora K Gammelgaard; Hans-Georg Sahl; Hans-Henrik Kristensen |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 328 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-28 Completed Date: 2010-06-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 1168-72 Citation Subset: IM |
Affiliation:
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Pharmaceutical Microbiology Section, Institute for Medical Microbiology, Immunology, and Parasitology, University of Bonn, D-53115 Bonn, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anti-Bacterial Agents
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pharmacology Ascomycota / chemistry Bacillus subtilis / drug effects, growth & development, metabolism*, ultrastructure Binding Sites Cell Membrane / metabolism Cell Wall / metabolism* Computer Simulation Defensins / metabolism*, pharmacology Fungal Proteins / metabolism*, pharmacology Models, Molecular Nuclear Magnetic Resonance, Biomolecular Oligonucleotide Array Sequence Analysis Peptides / metabolism*, pharmacology Protein Conformation Staphylococcus / drug effects, growth & development, metabolism*, ultrastructure Uridine Diphosphate N-Acetylmuramic Acid / analogs & derivatives*, metabolism Vancomycin / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Anti-Bacterial Agents; 0/Defensins; 0/Fungal Proteins; 0/Peptides; 0/Uridine Diphosphate N-Acetylmuramic Acid; 0/muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; 0/plectasin; 1404-90-6/Vancomycin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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