title: Determination of the three-dimensional structure of iberiotoxin in solution by 1H nuclear magnetic resonance spectroscopy.
abstract: The solution structure of chemically synthesized iberiotoxin, a scorpion toxin that blocks Ca(2+)-activated K+ channels, has been determined using 2D 1H NMR spectroscopy. Analysis of the NOEs, coupling constants, and HN-DN exchange rates indicates the structure consists of an antiparallel beta-sheet from residues 25 to 36, with a type 1 turn at residues 30-31, and a helix from residues 13 to 21. The carboxyl-terminal residues form a short, and distorted, third strand of the sheet. The NMR data are consistent with disulfide bonds from residues 7 to 28, 13 to 33, and 17 to 35. The disulfide bridging presents the same profile as in other scorpion toxins, where a Cys-X-Cys sequence in a strand of sheet forms two disulfide bonds to a Cys-X-X-X-Cys sequence in a helix. Three-dimensional structures were generated using the torsion angle space program PEGASUS. The best ten structures had an average rmsd over all pairwise comparisons of 1.49 A. The average rmsd to a calculated average structure is 1.0 A. The resulting structures appear very similar to those of charybdotoxin, a related scorpion toxin.
authors.affiliation: Department of Biophysical Chemistry, Merck Research Laboratory, Rahway, New Jersey 07065.
authors.forename: B A
authors.initials: BA
authors.lastname: Johnson
authors.forename: E E
authors.initials: EE
authors.lastname: Sugg
mesh_terms: D000595:Amino Acid Sequence; D018999:Charybdotoxin; D004220:Disulfides / Q000032:analysis; D006859:Hydrogen; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D012604:Scorpion Venoms / Q000737:chemistry*; D012689:Sequence Homology, Nucleic Acid
chemical_list: D004220:Disulfides; D010455:Peptides; D012604:Scorpion Venoms; D018999:Charybdotoxin; C064719:iberiotoxin; D006859:Hydrogen