Three-dimensional structure in lipid micelles of the pediocin-like antimicrobial peptide sakacin P and a sakacin P variant that is structurally stabilized by an inserted C-terminal disulfide bridge

Biochemistry. 2003 Oct 7;42(39):11417-26. doi: 10.1021/bi034572i.


The three-dimensional structures in dodecylphosphocholine (DPC) micelles and in trifluoroethanol (TFE) of the pediocin-like antimicrobial peptide sakacin P and an engineered variant of sakacin P (termed sakP[N24C+44C]) have been determined by use of nuclear magnetic resonance spectroscopy. SakP[N24C+44C] has an inserted non-native activity- and structure-stabilizing C-terminal disulfide bridge that ties the C-terminus to the middle part of the peptide. In the presence of DPC, the cationic N-terminal region (residues 1-17) of both peptides has an S-shaped conformation that is reminiscent of a three-stranded antiparallel beta-sheet and that is more pronounced when the peptide was dissolved in TFE instead of DPC. The four positively charged residues located in the N-terminal part are found pointing to the same direction. For both peptides, the N-terminal region is followed by a well-defined central amphiphilic alpha-helix (residues 18-33), and this in turn is followed by the C-terminal tail (residues 34-43 for sakacin P and 34-44 for sakP[N24C+44C]) that lacks any apparent common secondary structural motif. In the presence of DPC, the C-terminal tails in both peptides fold back onto the central alpha-helix, thereby creating a hairpin-like structure in the C-terminal halves. The lack of long-range NOEs between the beta-sheet Nu-terminal region and the hairpin-like C-terminal half indicates that there is a flexible hinge between these regions. We discuss which implications such a structural arrangement has on the interaction with the target cell membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / chemistry*
  • Bacteriocins / chemistry*
  • Bacteriocins / genetics*
  • Circular Dichroism
  • Disulfides / chemistry*
  • Lactobacillus / metabolism
  • Micelles
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides*
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / chemistry*
  • Protein Conformation
  • Protein Isoforms
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Structure-Activity Relationship
  • Trifluoroethanol / chemistry*


  • Anti-Bacterial Agents
  • Bacteriocins
  • Disulfides
  • Micelles
  • Peptides
  • Protein Isoforms
  • Recombinant Proteins
  • Phosphorylcholine
  • sakacin P protein, Lactobacillus
  • dodecylphosphocholine
  • Trifluoroethanol