Three-dimensional structure of omega-conotoxin GVIA determined by 1H NMR.

omega-Conotoxin GVIA, a peptide of 27 amino acid residues and three disulfide bridges, has been studied by NMR techniques. The complete assignment of the corresponding proton NMR spectra was performed by two-dimensional sequence specific methods at 288 K and pH 3.5. On the basis of 169 distance restraints derived from this analysis, the three-dimensional structure was obtained. A total of 30 initial structures were generated by distance geometry methods and further refined by restrained energy minimization techniques yielding a final set of 8 structures. The mean root-mean-square deviation between each of the 8 structures and the mean atomic coordinates for all residues is 0.82 +/- 0.06 A for the backbone atoms and 1.45 +/- 0.18 A for all non-H atoms. The structure shows a globular folding pattern that is stabilized by the three disulfide linkages and a number of intramolecular hydrogen bonds. A total of 14 hydroxyl groups are found at the periphery fully exposed to the solvent. These groups, together with the charged side chains of Lys and Arg residues emerging radially from the peptide core, provide specific recognition elements for the interaction of this toxin with neuronal calcium channels.