Some of our contributions to research on toxins from scorpion, spider, conus and fish venoms are given below. 

• We have purified a new family of conotoxins,λ-conotoxins.  They differ from α-conotoxins in their disulfide bonding pattern.   Because of their novel disulfide bonds they have a planar conformation compared to globular conformation.  This conformational difference results in 1300-fold higher biological activity. We identified the structural features determining alternative disulfide pairing in α- and λ/χ-conotoxins. We determined the NMR structures of CMrV, α λ/χ -conotoxins.

• We determined the structural features which determine the disulfide pairing and folding pattern of α -conotoxins α λ/χ -conotoxins. We used direct sequence comparison between these two families of toxins to identify the proline residue in the first cysteine loop and C-terminal amidation as major differences. Using a battery of synthetic peptides, we showed that both these structural features determine the folding pattern. This is the first report of such small changes that affect the disulfide pairing and hence the protein folds.

• We have purified new family of potassium channel blockers from scorpion venoms. They are structurally unrelated any known proteins. Based on their 3D structure, we studied the presence of lysine and phenylalanine dyad and predicted its ability to block the potassium channels. We have shown that these short peptides block Kv1.2 and Kv1.3 channels. We also described the importance of the dyad for its function.

• We have identified the functional site of the α- type of sodium channel toxins from scorpion venoms. The short peptide designed based on this site behaves similar to the parent toxin.

 

Key Publications