Cobratoxin Analysis

α-Cobratoxin is potent postsynaptic nicotinic acetylcholine receptor antagonist extracted from the venom of Thailand cobra species, naja nana siamensis (Eaker, Harris and Thesleff, 1971). Hence, it acts as a neuromuscular blocking agent by disrupting neurotransmission in the skeletal muscles by inhibiting the binding of acetylcholine. Binding take place in the ligand binding compartment found in-between the α/γ or α/δ of nicotinic acetylcholine receptor (nAChR) subunits. The secondary structure of cobra toxin comprises of β strands, with the essential residues for nAChR binding sites present in loop I and in the tip of loop II. Toxin residues namely R33 and F29 were mainly associated with interactions with acetylcholine receptors C187, Y185,

This neurotoxin plays its role by inhibiting the action of the Ca2+ activated voltage gated K+ Channels found in aortic smooth muscle cells and GH3 anterior pituitary cells. Hence, it is an high-affinity inhibitor of high-conductance due to its three disulphide bonds and conformational stability. By binding to the exterior interface of the channel protein, the positively charged residues of the toxin enables reversible blockage of the channel, which results in the hyper-excitability of the nervous system (Massefski et al., 1990). It acts by interacting with one of the four overlapping, yet independent binding sites which can either be closed or open conformations.The magnitude of the blockage is elevated by the decreased ionic strength. The block is occurred as a result of the binding of Asp 381 on the K+ Channels with the Asn 30 on the Charybdotoxin molecule (Goldstein and Miller,

Action potentials of several iso-forms of fast voltage-gated sodium channels are blocked, although the resting membrane resistance and potentials are restored at normal levels. According to the study by Chen and Chung (2014), suggested that positively charged guanidine group of the toxin extends and binds complementary to the two acidic residues of the distinctive DEKA ring localised at position 177, although the precise phenomena is not yet fully revealed. These acidic residues are found to significant in stabilising the network of hydrogen bonds. Axonal transmission is restricted by the toxin by inhibiting the sodium conduction at nodes of Ranvier, inhibiting muscle and nerve conductions. Its acts directly or approximately near chemoreceptor trigger zone causing vomiting. Paralysis of respiratory muscles and nerves or targeted action of the toxin on the respiratory centre results in respiratory depression(Karimi and Lari,