Structure and bactericidal activity of an antibiotic dodecapeptide purified from bovine neutrophils.
Cytoplasmic granules of neutrophils store a variety of cationic polypeptides, which exert in vitro a potent antibacterial action and are potentially involved in host defense mechanisms. From an acid extract of bovine neutrophil granules we have purified over 2,000-fold a dodecapeptide exhibiting bactericidal activity against both Escherichia coli and Staphylococcus aureus at 10(-7)-10(-5) M concentration. The purification procedure involved only two steps of ion-exchange and reversed-phase chromatography. The peptide, named bactenecin, has the amino acid sequence, Arg-Leu-Cys-Arg-Ile-Val-Val-Ile-Arg-Val-Cys-Arg, maintained in a cyclic structure by a disulfide bond between the two cysteine residues. Computer modeling of the dodecapeptide resulted in a conformation in which the chain adopts an antiparallel extended structure forming a gamma turn at residue 7.
Romeo
D
D
Department of Biochemistry, Biophysics, and Macromolecular Chemistry, University of Trieste, Italy.
Skerlavaj
B
B
Bolognesi
M
M
Gennaro
R
R
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D003594:Cytoplasmic Granules / Q000032:analysis; D004220:Disulfides / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000032:analysis*; D009842:Oligopeptides; D010456:Peptides, Cyclic / Q000302:isolation & purification* / Q000494:pharmacology; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000187:drug effects*; D013816:Thermodynamics
D000900:Anti-Bacterial Agents; D004220:Disulfides; D009842:Oligopeptides; D010456:Peptides, Cyclic; C056454:bactenecin