The solution structures and activity of caerin 1.1 and caerin 1.4 in aqueous trifluoroethanol and dodecylphosphocholine micelles.
The caerin 1 peptides are among the most powerful of the broad-spectrum antibiotic amphibian peptides. Caerin 1.1 has previously been shown to form an amphipathic helix-bend-helix structure in aqueous trifluoroethanol (H. Wong, J. H. Bowie, and J. A. Carver European Journal Biochemistry, 1997, Vol. 247, pp. 545-557) and structure-activity relationship studies indicate that both helices are required for activity, as well as flexibility in the bend region connecting the two. The structure of caerin 1.1 in dodecylphosphocholine micelles was investigated and shown to be very similar to that determined in aqueous trifluoroethanol. Caerin 1.4, which is identical to caerin 1.1, but with serine residues replacing Val5 and Gly7, is less active than caerin 1.1 against most bacterial species but has improved activity against Escherichia coli and Micrococcus luteus. The solution NMR structure of caerin 1.4 was determined in both aqueous trifluoroethanol and dodecylphosphocholine micelles, and was shown to be similar to caerin 1.1. It was concluded that differences in the hydrophobicity and hydrophilic angle of the first helix are probably responsible for the different spectra of antibacterial activity. The similarity of the structures calculated in aqueous trifluoroethanol and dodecylphosphocholine micelles suggests that, for caerin 1.1 and 1.4, these solvent systems are equally as good at representing a membrane environment.
Wegener
Kate L
KL
Department of Chemistry, The University of Adelaide, Australia.
Carver
John A
JA
Bowie
John H
JH
D000595:Amino Acid Sequence; D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D012996:Solutions; D013329:Structure-Activity Relationship
D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; D012996:Solutions; C107616:caerin 1.1, Anura; C475101:caerin 1.4 protein, Litoria