title: Solution structure of alpha-conotoxin MI determined by 1H-NMR spectroscopy and molecular dynamics simulation with the explicit solvent water.
abstract: The conformation of alpha-conotoxin MI, a potent antagonist of the nicotinic acetylcholine receptor, has been investigated in aqueous solution. Two-dimensional NMR experiments and simulated annealing calculations provide the overall topology of alpha-conotoxin MI; then molecular dynamics simulation with the explicit solvent water was followed in order to obtain a more reliable solution structure. The resulting conformation indicates the presence of a 3(10) helix and a type I beta-turn for residues Pro6-Cys8 and Gly9-Try12, respectively, and shows a significant structural similarity to that of alpha-conotoxin GI, which has biological activity similar to that of MI. The present study provides a molecular basis for the alpha-conotoxin-receptor interaction.
authors.affiliation: School of Pharmaceutical Sciences, Kitasato University, Shirokane, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Gouda
authors.forename: K
authors.initials: K
authors.lastname: Yamazaki
authors.forename: J
authors.initials: J
authors.lastname: Hasegawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Nishiuchi
authors.forename: S
authors.initials: S
authors.lastname: Sakakibara
authors.forename: S
authors.initials: S
authors.lastname: Hirono
mesh_terms: D003198:Computer Simulation; D020916:Conotoxins; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008978:Mollusk Venoms / Q000737:chemistry*; D018733:Nicotinic Antagonists / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011978:Receptors, Nicotinic / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014867:Water
chemical_list: D020916:Conotoxins; D008978:Mollusk Venoms; D018733:Nicotinic Antagonists; D010456:Peptides, Cyclic; D011978:Receptors, Nicotinic; D014867:Water; C029960:conotoxin GI; C036155:conotoxin MI