title: The 1.1 A crystal structure of the neuronal acetylcholine receptor antagonist, alpha-conotoxin PnIA from Conus pennaceus.
abstract: BACKGROUND
  alpha-Conotoxins are peptide toxins, isolated from Conus snails, that block the nicotinic acetylcholine receptor (nAChR). The 16-residue peptides PnIA and PnIB from Conus pennaceus incorporate the same disulfide framework as other alpha-conotoxins but differ in function from most alpha-conotoxins by blocking the neuronal nAChR, rather than the skeletal muscle subtype. The crystal structure determination of PnIA was undertaken to identify structural and surface features that might be important for biological activity.
  
  
  RESULTS
  The 1.1 A crystal structure of synthetic PnIA was determined by direct methods using the Shake-and-Bake program. The three-dimensional structure incorporates a beta turn followed by two alpha-helical turns. The conformation is stabilised by two disulfide bridges that form the interior of the molecule, with all other side chains oriented outwards.
  
  
  CONCLUSIONS
  The compact architecture of the PnIA toxin provides a rigid framework for presentation of chemical groups that are required for activity. The structure is characterized by distinct hydrophobic and polar surfaces; a 16 A separation of the sole positive and negative charges (these two charged residues being located at opposite ends of the molecule); a hydrophobic region and a protruding tyrosine side chain. These features may be important for the specific interaction of PnIA with neuronal nAChR.
authors: Centre for Drug Design and Development, University of Queensland, St Lucia, Australia.
authors: S H
authors: SH
authors: Hu
authors: J
authors: J
authors: Gehrmann
authors: L W
authors: LW
authors: Guddat
authors: P F
authors: PF
authors: Alewood
authors: D J
authors: DJ
authors: Craik
authors: J L
authors: JL
authors: Martin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018680:Cholinergic Antagonists / Q000737:chemistry; D020916:Conotoxins; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008978:Mollusk Venoms; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D012908:Snails / Q000737:chemistry*
chemical_list: D018680:Cholinergic Antagonists; D020916:Conotoxins; D008978:Mollusk Venoms; D009842:Oligopeptides; C089038:alpha-conotoxin PnIA