title: Three-dimensional structure of the alpha-conotoxin GI at 1.2 A resolution.
abstract: Predatory marine snails of the genus Conus paralyze their fish prey by injecting a potent toxin. The alpha-conotoxin GI is a 13-residue peptide isolated from venom of Conus geographus. It functions by blocking the postsynaptic nicotinic acetylcholine receptor. After crystallization in deionized water, the three-dimensional structure of the GI neurotoxin was determined to 1.2 A resolution by X-ray crystallography. This structure, which can be described as a triangular slab, shows overall similarities to those derived by NMR, CD, and predictive methods. The principal framework of the molecule is provided by two disulfide bonds, one linking Cys 2 and Cys 7 and the other Cys 3 and Cys 13. Opposite ends of the sequence are drawn together even further by hydrogen bonds between Glu 1 and Cys 13 and between Cys 2 and Ser 12. Since the C-terminus is amidated, only one negative charge is present (carboxylate of Glu 1), and this is not implicated in receptor binding. Two positively charged regions (the alpha-amino group of Glu 1 and the guanido group of Arg 9) are situated 15 A apart at the corners of the triangular face of the molecule. phi, psi angles characteristic of a 3(10) helix were observed for residues 5-7. For residues 8-11, these angles were consistent with either a type I beta-turn or a distorted 3(10) helix.
authors.affiliation: Centre for Drug Design and Development, University of Queensland, St. Lucia, Australia.
authors.forename: L W
authors.initials: LW
authors.lastname: Guddat
authors.forename: J A
authors.initials: JA
authors.lastname: Martin
authors.forename: L
authors.initials: L
authors.lastname: Shan
authors.forename: A B
authors.initials: AB
authors.lastname: Edmundson
authors.forename: W R
authors.initials: WR
authors.lastname: Gray
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry*; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012908:Snails; D014867:Water / Q000378:metabolism
chemical_list: D020916:Conotoxins; D004220:Disulfides; D008978:Mollusk Venoms; D018733:Nicotinic Antagonists; D010455:Peptides; D010456:Peptides, Cyclic; D014867:Water; C029960:conotoxin GI