Solution structure of alpha-conotoxin MI determined by 1H-NMR spectroscopy and molecular dynamics simulation with the explicit solvent water

Biochim Biophys Acta. 1997 Dec 5;1343(2):327-34. doi: 10.1016/s0167-4838(97)00140-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Conotoxins*
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Models, Molecular
  • Mollusk Venoms / chemistry*
  • Nicotinic Antagonists / chemistry*
  • Nicotinic Antagonists / metabolism
  • Nicotinic Antagonists / pharmacology
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / pharmacology
  • Protein Conformation*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Receptors, Nicotinic / metabolism
  • Sequence Homology, Amino Acid
  • Water

Substances

  • Conotoxins
  • Mollusk Venoms
  • Nicotinic Antagonists
  • Peptides, Cyclic
  • Receptors, Nicotinic
  • Water
  • conotoxin GI
  • conotoxin MI