STRUCTURE, FUNCTION AND FOLDING OF THREE FINGER TOXINS

Three finger toxins (3FTxs) are one of the family of peptides in snake venom. Despite the common protein fold, they exhibit diverse pharmacological activities. Our group characterized Oh9-1, a neurotoxin from venom of Ophiophagus hannah. Although Oh9-1 binds to the same acetylcholine binding pocket as the -neurotoxins, it lacks key functional residues. In this thesis, I describe the three-dimensional structure of Oh9-1 by NMR. Unlike the above class of postsynaptic neurotoxins, we identified a 3FTx that acts at the presynaptic site. This toxin, isolated from venom of Micrurus fulvius, was named as “presynapsin”. Systemic sequence investigation was done to understand the functional diversity. Finally, I attempted to determine the structural elements that assist in the native disulphide pairings which help in maintaining the canonical 3FTx-fold. I have evaluated the role of primary sequence and secondary structures to define the molecular determinants that govern the disulphide pairing.

Author dc:creator

• PUDUR VENKATESWARULU DILEEP KUMAR

• Three finger toxins, NMR, Solid phase peptide synthesis, Structure, Cysteine rich peptides, oxidative refolding