Structure-activity relationships of mu-conotoxin GIIIA: structure determination of active and inactive sodium channel blocker peptides by NMR andsimulated annealing calculations

The structure-activity correlates of the sodium channel blocker peptidemu-conotoxin GIIIA was investigated by nuclear magnetic resonance studies and simulated annealing computations of an inactive analog. Results indicate that activity of the peptide was influenced by direct interaction of an important arginine residue with the sodium channel molecules. The active site was characterized by a cluster of arginine, lysine and hydroxyproline which interacts with the receptor site of the sodium channel. The hydroxyl group of hydroxyproline shares a common channel site with tetrodoxin and saxitoxin.