title: Structure-activity relationships in the peptide antibiotic nisin: antibacterial activity of fragments of nisin.
abstract: The post-translationally modified peptide antibiotic nisin has been cleaved by a number of proteases and the fragments produced purified, characterised chemically, and assayed for activity in inhibiting the growth of Lactococcus lactis MG1614 and Micrococcus luteus NCDO8166. These results provide information on the importance of different parts of the nisin molecule for its growth-inhibition activity. Removal of the C-terminal five residues leads to approximately a 10-fold decrease in potency, while removal of a further nine residues, encompassing two of the lanthionine rings, leads to a 100-fold decrease. There are some differences between analogous fragments of nisin and subtilin, suggesting possible subtle differences in mode of action. Cleavage within, or removal of, lanthionine ring C essentially abolishes the activity of nisin. The fragment nisin1-12 is inactive itself, and specifically antagonises the growth-inhibitory action of nisin. These results are discussed in terms of current models for the mechanism of action of nisin.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nottingham, UK.
authors.forename: W C
authors.initials: WC
authors.lastname: Chan
authors.forename: M
authors.initials: M
authors.lastname: Leyland
authors.forename: J
authors.initials: J
authors.lastname: Clark
authors.forename: H M
authors.initials: HM
authors.lastname: Dodd
authors.forename: L Y
authors.initials: LY
authors.lastname: Lian
authors.forename: M J
authors.initials: MJ
authors.lastname: Gasson
authors.forename: B W
authors.initials: BW
authors.lastname: Bycroft
authors.forename: G C
authors.initials: GC
authors.lastname: Roberts
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins; D001430:Bacteriocins; D013294:Lactococcus lactis / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D016982:Micrococcus luteus / Q000187:drug effects / Q000254:growth & development; D008954:Models, Biological; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009561:Nisin / Q000737:chemistry* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology*; D010455:Peptides; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins; D010446:Peptide Fragments; D010455:Peptides; D009561:Nisin; C002836:subtilin