Regular Article

Solution structure of the cyclic peptide contryphan-Vn, a Ca2+-dependent K+ channel modulator

  1. Tommaso Eliseo1,
  2. Daniel Oscar Cicero2,
  3. Cristina Romeo3,
  4. Maria Eugenia Schininà3,
  5. Gabriella Raybaudi Massilia4,
  6. Fabio Polticelli4,
  7. Paolo Ascenzi4,5,
  8. Maurizio Paci2,*

Article first published online: 1 APR 2004

DOI: 10.1002/bip.20025

Issue

Biopolymers

Biopolymers

Volume 74, Issue 3, pages 189–198, 15 June 2004

Additional Information

How to Cite

Eliseo, T., Cicero, D. O., Romeo, C., Schininà, M. E., Massilia, G. R., Polticelli, F., Ascenzi, P. and Paci, M. (2004), Solution structure of the cyclic peptide contryphan-Vn, a Ca2+-dependent K+ channel modulator. Biopolymers, 74: 189–198. doi: 10.1002/bip.20025

Author Information

  1. 1

    Department of Chemistry, University of Rome “La Sapienza,” Piazzale Aldo Moro 5, 00198 Rome, Italy

  2. 2

    INFM and Department of Chemical Sciences and Technologies, University of Rome “Tor Vergata,” Via della Ricerca Scientifica, 00133 Rome, Italy

  3. 3

    Department of Biochemical Sciences, University of Rome “La Sapienza,” Piazzale Aldo Moro 5, 00198 Rome, Italy

  4. 4

    Department of Biology, University “Roma Tre,” Viale Guglielmo Marconi, 446, 00146 Rome, Italy

  5. 5

    Interdepartmental Laboratory for Electron Microscopy, University “Roma Tre” Via della Vasca Navale, 79, 00146 Rome,Italy

*Department of Chemical Sciences and Technologies, University of Rome “Tor Vergata,” Via della Ricerca Scientifica, 00133 Rome, Italy

Publication History

  1. Issue published online: 12 MAY 2004
  2. Article first published online: 1 APR 2004
  3. Manuscript Accepted: 17 DEC 2003
  4. Manuscript Received: 9 MAY 2003

Funded by

  • Ministero dell'Istruzione, dell'Università e della Ricerca of Italy

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (176K)

Keywords:

  • contryphan;
  • NMR;
  • cyclic peptides;
  • three-dimensional structure

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. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004

View Full Article (HTML) Get PDF (176K)