title: Eurocin, a new fungal defensin: structure, lipid binding, and its mode of action.
abstract: Antimicrobial peptides are a new class of antibiotics that are promising for pharmaceutical applications because they have retained efficacy throughout evolution. One class of antimicrobial peptides are the defensins, which have been found in different species. Here we describe a new fungal defensin, eurocin. Eurocin acts against a range of Gram-positive human pathogens but not against Gram-negative bacteria. Eurocin consists of 42 amino acids, forming a cysteine-stabilized α/β-fold. The thermal denaturation data point shows the disulfide bridges being responsible for the stability of the fold. Eurocin does not form pores in cell membranes at physiologically relevant concentrations; it does, however, lead to limited leakage of a fluorophore from small unilamellar vesicles. Eurocin interacts with detergent micelles, and it inhibits the synthesis of cell walls by binding equimolarly to the cell wall precursor lipid II.
authors.affiliation: Department of Biotechnology, Chemistry, and Environmental Engineering, Aalborg University, Sohngaardsholmsvej 49, DK-9000 Aalborg, Denmark.
authors.forename: Jesper S
authors.initials: JS
authors.lastname: Oeemig
authors.forename: Carina
authors.initials: C
authors.lastname: Lynggaard
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Knudsen
authors.forename: Frederik T
authors.initials: FT
authors.lastname: Hansen
authors.forename: Kent D
authors.initials: KD
authors.lastname: Nørgaard
authors.forename: Tanja
authors.initials: T
authors.lastname: Schneider
authors.forename: Brian S
authors.initials: BS
authors.lastname: Vad
authors.forename: Dorthe H
authors.initials: DH
authors.lastname: Sandvang
authors.forename: Line A
authors.initials: LA
authors.lastname: Nielsen
authors.forename: Søren
authors.initials: S
authors.lastname: Neve
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Kristensen
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Sahl
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Otzen
authors.forename: Reinhard
authors.initials: R
authors.lastname: Wimmer
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D023082:Defensins / Q000737:chemistry* / Q000494:pharmacology; D055325:Eurotium / Q000737:chemistry*; D005656:Fungal Proteins / Q000737:chemistry* / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000254:growth & development / Q000378:metabolism; D016908:Gram-Positive Bacterial Infections / Q000378:metabolism; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D008823:Micelles; D017510:Protein Folding; D017433:Protein Structure, Secondary; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D023082:Defensins; D005656:Fungal Proteins; D008563:Membrane Lipids; D008823:Micelles; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol