title: Stable isotope-assisted NMR characterization of interaction between lipid A and sarcotoxin IA, a cecropin-type antibacterial peptide.
abstract: Sarcotoxin IA is a 39-residue cecropin-type peptide from Sarcophaga peregrina. This peptide exhibits antibacterial activity against Gram-negative bacteria through its interaction with lipid A, a core component of lipopolysaccharides. To acquire detailed structural information on this specific interaction, we performed NMR analysis using bacterially expressed sarcotoxin IA analogs with (13)C- and (15)N-labeling along with lipid A-embedding micelles composed of dodecylphosphocholine. By inspecting the stable isotope-assisted NMR data, we revealed that the N-terminal segment (Leu3-Arg18) of sarcotoxin IA formed an amphiphilic α-helix upon its interaction with the aqueous micelles. Furthermore, chemical shift perturbation data indicated that the amino acid residues displayed on this α-helix were involved in the specific interaction with lipid A. On the basis of these data, we successfully identified Lys4 and Lys5 as key residues in the interaction with lipid A and the consequent antibacterial activity. Therefore, these results provide unique information for designing chemotherapeutics based on antibacterial peptide structures.
authors: Institute for Molecular Science and Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
authors: Maho
authors: M
authors: Yagi-Utsumi
authors: Yoshiki
authors: Y
authors: Yamaguchi
authors: Pornthip
authors: P
authors: Boonsri
authors: Takeshi
authors: T
authors: Iguchi
authors: Kazuo
authors: K
authors: Okemoto
authors: Shunji
authors: S
authors: Natori
authors: Koichi
authors: K
authors: Kato
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002247:Carbon Isotopes / Q000737:chemistry; D019476:Insect Proteins / Q000737:chemistry*; D007553:Isotope Labeling; D008050:Lipid A / Q000737:chemistry*; D008969:Molecular Sequence Data; D009587:Nitrogen Isotopes / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002247:Carbon Isotopes; D019476:Insect Proteins; D008050:Lipid A; D009587:Nitrogen Isotopes; C054733:sarcotoxin IA protein, Sarcophaga peregrina