title: Solution structure of the cyclic peptide contryphan-Vn, a Ca2+-dependent K+ channel modulator.
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 beta-turn from Gly 1 to Lys 6 and a type I beta-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.
authors.affiliation: Department of Chemistry, University of Rome La Sapienza, Piazzale Aldo Moro 5, 00198 Rome, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Eliseo
authors.forename: Daniel Oscar
authors.initials: DO
authors.lastname: Cicero
authors.forename: Cristina
authors.initials: C
authors.lastname: Romeo
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Schininà
authors.forename: Gabriella Raybaudi
authors.initials: GR
authors.lastname: Massilia
authors.forename: Fabio
authors.initials: F
authors.lastname: Polticelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Paci
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008978:Mollusk Venoms / Q000737:chemistry / Q000378:metabolism; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D012908:Snails / Q000737:chemistry / Q000378:metabolism
chemical_list: D008978:Mollusk Venoms; D010456:Peptides, Cyclic; D024681:Potassium Channels, Calcium-Activated; C102355:contryphan; D011188:Potassium; D002118:Calcium