Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/31593
Title: Structural and Functional Characterization of Haditoxin, a novel neurotoxin isolated from the venom of Ophiohagus Hannah (King Cobra)
Authors: AMRITA ROY
Keywords: Protein, Neurotoxin, Structure, Function, Snake, Venom
Issue Date: 19-Aug-2011
Source: AMRITA ROY (2011-08-19). Structural and Functional Characterization of Haditoxin, a novel neurotoxin isolated from the venom of Ophiohagus Hannah (King Cobra). ScholarBank@NUS Repository.
Abstract: Snake venoms are a rich source of bioactive proteins and polypeptides with a wide variety of molecular targets. Because of their high specificity and affinity, some of these molecules have contributed significantly to the development of molecular probes and therapeutic leads. In continuation of our efforts in the characterization of novel snake venom toxins we have identified and characterized a novel non-covalent homodimeric neurotoxin, haditoxin from the venom of Ophiophagus hannah (King cobra). Haditoxin was first identified in a cDNA library of O. hannah venom gland tissue. The protein was isolated from the crude venom using a two-step chromatographic approach. Haditoxin exhibited novel pharmacology with antagonism towards muscle (alpha beta gamma delta) and neuronal (alpha7, alpha3beta2 and alpha4beta2) nicotinic acetylcholine receptors (nAChRs), with highest affinity for alpha7-nAChRs. Moreover, unlike the small molecular ligands, haditoxin is specific for nAChRs and not to other ligand-gated ion channel receptors as well as invertebrate nicotinic receptor homologs. The biophysical studies as well as the crystal structure indicated the existence of the protein as a non-covalent homodimer. The monomeric subunits of haditoxin are similar to short chain alpha-neurotoxins, whereas the quaternary structure is similar to that of kappa-neurotoxins such as kappa-bungarotoxin. Interestingly, haditoxin exhibited unique high affinity blockade on alpha7-nAChRs, which is recognized by neither short chain alpha-neurotoxins nor kappa-neurotoxins. This is the first report of a dimeric three-finger neurotoxin interacting with the muscle nAChR as well as the first short-chain alpha-neurotoxin to interact with neuronal alpha7-nAChR with nanomolar affinity.
URI: http://scholarbank.nus.edu.sg/handle/10635/31593
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