title: Structure and dynamics of the lantibiotic mutacin 1140.
abstract: Mutacin 1140 is a member of a family of ribosomally synthesized peptide bacteriocins called lantibiotics (lanthionine-containing antibiotics) and is produced by the Gram-positive bacterium Streptococcus mutans. Mutacin 1140 has been shown to be effective against a broad array of Gram-positive bacteria. Chromatography and mass spectroscopy data suggested that mutacin 1140 forms a small compact structure. Nuclear magnetic resonance (NMR) data and restrained molecular dynamics simulations showed that mutacin 1140 interconverts between multiple structures. Calculations of scalar (J) coupling constants showed the best agreement with experimental values when the entire population-weighted ensemble of structures was used, providing independent support for the ensemble. Representative structures from each major group in the ensemble had a common feature in which they are all kinked around the hinge region forming a horseshoe-like shape, and the regions of flexibility of the molecule were limited and well-defined. The structures determined in this study provide a starting point for modeling the mutacin 1140-membrane interactions and pore formation.
authors.affiliation: University of Florida Interdisciplinary Graduate Program in Neuroscience, Gainesville, Florida 32611, USA.
authors.forename: Leif
authors.initials: L
authors.lastname: Smith
authors.forename: Cherian
authors.initials: C
authors.lastname: Zachariah
authors.forename: Ramanan
authors.initials: R
authors.lastname: Thirumoorthy
authors.forename: Jim
authors.initials: J
authors.lastname: Rocca
authors.forename: Jan
authors.initials: J
authors.lastname: Novák
authors.forename: J D
authors.initials: JD
authors.lastname: Hillman
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Edison
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism*; D001430:Bacteriocins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002850:Chromatography, Gel; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides; D011487:Protein Conformation
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D010455:Peptides; C112560:mutacin 1140