Evidence for phenylalanine zipper-mediated dimerization in the X-ray crystal structure of a magainin 2 analogue

J Am Chem Soc. 2013 Oct 23;135(42):15738-15741. doi: 10.1021/ja409082w. Epub 2013 Oct 8.

Abstract

High-resolution structure elucidation has been challenging for the large group of host-defense peptides that form helices on or within membranes but do not manifest a strong folding propensity in aqueous solution. Here we report the crystal structure of an analogue of the widely studied host-defense peptide magainin 2. Magainin 2 (S8A, G13A, G18A) is a designed variant that displays enhanced antibacterial activity relative to the natural peptide. The crystal structure of magainin 2 (S8A, G13A, G18A), obtained for the racemic form, features a dimerization mode that has previously been proposed to play a role in the antibacterial activity of magainin 2 and related peptides.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacillus subtilis / drug effects
  • Crystallography, X-Ray
  • Dimerization
  • Dose-Response Relationship, Drug
  • Enterococcus faecium / drug effects
  • Escherichia coli / drug effects
  • Magainins / chemical synthesis
  • Magainins / chemistry
  • Magainins / metabolism*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Phenylalanine / chemistry*
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship
  • Xenopus Proteins / chemical synthesis
  • Xenopus Proteins / chemistry
  • Xenopus Proteins / metabolism*

Substances

  • Anti-Bacterial Agents
  • Magainins
  • Xenopus Proteins
  • magainin 2 peptide, Xenopus
  • Phenylalanine

Associated data

  • PDB/4MGP