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

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