Structure and dynamics of the lantibiotic mutacin 1140

Biochemistry. 2003 Sep 9;42(35):10372-84. doi: 10.1021/bi034490u.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / metabolism*
  • Bacteriocins / chemistry*
  • Bacteriocins / genetics
  • Bacteriocins / metabolism*
  • Chromatography, Gel
  • Mass Spectrometry
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Weight
  • Peptides*
  • Protein Conformation

Substances

  • Anti-Bacterial Agents
  • Bacteriocins
  • Peptides
  • mutacin 1140