title: Conformational analysis of a 20-membered cyclic peptide disulfide from Conus virgo with a WPW segment: evidence for an aromatic-proline sandwich.
abstract: A novel peptide containing a single disulfide bond, CIWPWC (Vi804), has been isolated and characterised from the venom of the marine cone snail, Conus virgo. A precursor polypeptide sequence derived from complementary DNA, corresponding to the M-superfamily conotoxins, has been identified. The identity of the synthetic and natural peptide sequence has been established. A detailed analysis of the conformation in solution is reported for Vi804 and a synthetic analogue, CI(D) WPWC ((D) W3-Vi804), in order to establish the structure of the novel WPW motif, which occurs in the context of a 20-membered macrocyclic disulfide. Vi804 exists exclusively in the cis W3P4 conformer in water and methanol, whereas (D) W3-Vi804 occurs exclusively as the trans conformer. NMR spectra revealed a W3P4 type VI β turn in Vi804 and a type II' β turn in the analogue peptide, (D) W3-Vi804. The extremely high-field chemical shifts of the proline ring protons, together with specific nuclear Overhauser effects, are used to establish a conformation in which the proline ring is sandwiched between the flanking Trp residues, which emphasises a stabilising role for the aromatic-proline interactions, mediated predominantly by dispersion forces.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012 (India), Fax: (+91) 80-3600683; NMR Research Centre, Indian Institute of Science, Bangalore 560012 (India).
authors.forename: Rajesh
authors.initials: R
authors.lastname: Sonti
authors.forename: K N Shashanka
authors.initials: KN
authors.lastname: Rao
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Chidanand
authors.forename: Konkallu Hanumae
authors.initials: KH
authors.lastname: Gowd
authors.forename: Srinivasarao
authors.initials: S
authors.lastname: Raghothama
authors.forename: Padmanabhan
authors.initials: P
authors.lastname: Balaram
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D052078:Conus Snail / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D017433:Protein Structure, Secondary; D016415:Sequence Alignment
chemical_list: D004220:Disulfides; D010456:Peptides, Cyclic; D011392:Proline
keywords: amino acids; aromatic-proline interactions; beta turns; disulfides; peptides