Solution structure of the cyclic peptide contryphan-Vn, a Ca 2+-dependent K+ channel modulator

Tommaso Eliseo, Daniel Oscar Cicero, Cristina Romeo, Maria Eugenia Schininà, Gabriella Raybaudi Massilia, Fabio Polticelli, Paolo Ascenzi, Maurizio Paci

Research output: Contribution to journalArticlepeer-review

Abstract

The solution structure of contryphan-Vn, a cyclic peptide with a double cysteine S-S bridge and containing a D-tryptophan extracted from the venom of the cone snail Conus ventricosus, has been determined by NMR spectroscopy using a variety of homonuclear and heteronuclear NMR methods and restrained molecular dynamics simulations. The main conformational features of backbone contryphan-Vn are a type IV β-turn from Gly 1 to Lys 6 and a type I β-turn from Lys 6 to Cys 9. As already found in other contryphans, one of the two prolines-the Pro4-is mainly in the cis conformation while Pro7 is trans. A small hydrophobic region probably partly shielded from solvent constituted from the close proximity of side chains of Pro7 and Trp8 was observed together with a persistent salt bridge between Asp2 and Lys6, which has been revealed by the diagnostic observation of specific nuclear Overhauser effects. The salt bridge was used as a restraint in the molecular dynamics in vacuum but without inserting explicit electrostatic contribution in the calculations. The backbone of the unique conformational family found of contryphan-Vn superimposes well with those of contryphan-Sm and contryphan-R. This result indicates that the contryphan structural motif represents a robust and conserved molecular scaffold whose main structural determinants are the size of the intercysteine loop and the presence and location in the sequence of the D-Trp and the two Pro residues.

Original languageEnglish
Pages (from-to)189-198
Number of pages10
JournalBiopolymers
Volume74
Issue number3
DOIs
Publication statusPublished - Jun 15 2004

Keywords

  • Contryphan
  • Cyclic peptides
  • NMR
  • Three-dimensional structure

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biophysics

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