lanthiopeptin and lysophosphatidylethanolamine

The three-dimensional structure of a complex of cinnamycin, a 19-amino acid residue immunopotentiator peptide, and lysophosphatidylethanolamine was determined by 1H-NMR. The complex was cylindrical in shape, 11 A in diameter and 26 A in length, excluding the acyl chain of the phospholipid. The peptide had a hydrophobic pocket surrounded by residues Phe-7 through Ala(S)-14 to bind to the head group of the ligand. Fitting of the head group to the hydrophobic pocket was so good that other than a glycerophosphoethanolamine head group would be unable to fit the pocket. The goodness of the fitting is compatible with the strict specificity of ligand binding of the peptide.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Bacteriocins; Lysophospholipids; Magnetic Resonance Spectroscopy; Molecular Sequence Data; Molecular Structure; Peptides, Cyclic; Protons

Ro09-0198 is a peptide antibiotic and immunopotentiator produced by Streptoverticillium griseoverticillatum which exhibits antitumor and antimicrobial activities. The chemical structure has been determined [Kessler et al. (1988) Helv. Chim. Acta 71, 1924-1929; Wakamiya et al. (1988) Tetrahedron Lett. 37, 4771-4772]. This peptide specifically interacts with (lyso)phosphatidylethanolamine, causing hemolysis and enhancing permeability in phosphatidylethanolamine-containing vesicles [Choung et al. (1988) Biochim. Biophys. Acta 940, 171-179, 180-187]. The highly specific nature of the interaction was studied by two dimensional proton NMR analyses. Proton resonances of the peptide were observed in dimethyl sulfoxide solution in the presence of 1-dodecanoyl-sn-glycerophosphoethanolamine. By comparison to the chemical shifts in the absence of lysophosphatidylethanolamine and by analysis of intermolecular cross-peaks in NOESY spectra, amino acid residues involved in the binding with the phospholipid were identified. The ammonium group of the phospholipid interacts with the carboxylate group of beta-hydroxyaspartic acid-15 but not with that of the carboxylate terminus. The secondary ammonium group of lysinoalanine-19/6 is probably bound to the phosphate group of the lipid. The peptide does not interact strongly with the fatty acid chain of the lipid. A folded structure of the central part [from Phe7 to Ala(S)14] of the peptide opens on binding with the phospholipid and accommodates the glycerophosphoethanolamine head group.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Carbon Isotopes; Dimethyl Sulfoxide; Lysophospholipids; Magnetic Resonance Spectroscopy; Molecular Sequence Data; Peptides; Peptides, Cyclic; Phosphatidylethanolamines; Protein Binding; Protons; Solutions; Streptomycetaceae