SOLUTION STRUCTURE OF THE CALCIUM-CHANNEL ANTAGONIST OMEGA-CONOTOXIN GVIA

The three-dimensional solution structure is reported for omega-conotox in GVIA, which is a potent inhibitor of presynaptic calcium channels i n vertebrate neuromuscular junctions. Structures were generated by a h ybrid distance geometry and restrained molecular dynamics approach usi ng interproton distance, torsion angle, and hydrogen-bonding constrain ts derived from H-1 NMR data. Conformations of GVIA with low constrain t violations converged to a common peptide fold. The secondary structu re in the peptide is an antiparallel triple-stranded beta-sheet contai ning a beta-hairpin and three tight turns. The NMR data are consistent with the region of the peptide from residues S9 to C16 being more dyn amic than the rest of the peptide. The peptide has an amphiphilic stru cture with a positively charged hydrophilic side and an opposite side that contains a small hydrophobic region. Residues that are thought to be important in binding and function are located on the hydrophilic f ace of the peptide.