title: Solution structure of the antimicrobial peptide ranalexin and a study of its interaction with perdeuterated dodecylphosphocholine micelles.
abstract: Ranalexin, a 20-residue peptide isolated from the skin of the bullfrog Rana catesbeiana displays antimicrobial activity. This peptide contains two cysteine residues in positions 14 and 20 linked by a disulphide bridge. Ranalexin was chemically synthesised and close antimicrobial activities were measured for the reduced and oxidised forms. The solution structure of ranalexin was determined by using circular dichroism, proton NMR spectroscopy and molecular modelling techniques. The reduced and oxidised forms of ranalexin are mainly unstructured in water but display an alpha-helical structure spanning residues 8-15 and 8-17, respectively, in a trifluoroethanol/water mixture (3:7, by vol.). Ranalexin was found to interact with micelles of dodecylphosphocholine and to adopt a similar helical structure. Moreover, slow-exchanging amide protons located on the same side of the helix suggest that the hydrophobic face of the helix lies on the micelle surface. Hydrophobic residues of the poorly structured N-terminal part which are important for the biological activity are also involved in the interaction with micelles. Taken together, the results suggest that the disulphide bond does not strongly affect either the conformation or the antimicrobial activity of ranalexin.
authors.affiliation: Centre de Biochimie Structurale, UMR 9955, U414 INSERM, Université Montpellier 1, Faculté de Pharmacie, France.
authors.forename: E
authors.initials: E
authors.lastname: Vignal
authors.forename: A
authors.initials: A
authors.lastname: Chavanieu
authors.forename: P
authors.initials: P
authors.lastname: Roch
authors.forename: L
authors.initials: L
authors.lastname: Chiche
authors.forename: G
authors.initials: G
authors.lastname: Grassy
authors.forename: B
authors.initials: B
authors.lastname: Calas
authors.forename: A
authors.initials: A
authors.lastname: Aumelas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002942:Circular Dichroism; D003545:Cysteine / Q000737:chemistry; D003903:Deuterium; D004926:Escherichia coli / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011892:Rana catesbeiana; D012867:Skin / Q000737:chemistry; D012996:Solutions; D013212:Staphylococcus epidermidis / Q000187:drug effects; D014270:Trifluoroethanol; D014867:Water
chemical_list: D000900:Anti-Bacterial Agents; D008823:Micelles; D010456:Peptides, Cyclic; D012996:Solutions; D014867:Water; D010767:Phosphorylcholine; C086618:ranalexin; C028810:dodecylphosphocholine; D014270:Trifluoroethanol; D003903:Deuterium; D003545:Cysteine