Cobratoxin

α-Cobratoxin is a substance of the venom of certain Naja cobras. It is a muscle-type nicotinic acetylcholine receptor (nAChR) antagonist, which causes paralysis by preventing the binding of acetylcholine to the nAChR.

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Source

α-Cobratoxin is a neurotoxin from the venom of certain Naja cobras, such as Naja atra and Naja siamensis (the monocled cobra) (Yang, 1965).

Chemistry

α-Cobratoxin consists of 71 amino acid residues and 5 disulfide bridges (Zeng et al, 1965). It is also known as long neurotoxin 1, neurotoxin 3, or CbTx. It belongs to the type II alpha-neurotoxin subfamily, which also includes alpha-bungarotoxin.

Target

Cobratoxin binds with high affinity to ligand gated nicotinic acetylcholine receptor (nAChR) , which play an important role in synaptic transmission both in the central nervous system and at the neuromuscular junction (NMJ) (Konstantakaki et al, 2007). It has an affinity for the chick neuronal α7 nAChR of 6 nM and for the nAchR from the Torpedo NMJ of 39 pM (Servent, 2000).

Mode of action

Cobratoxin binds to the ligand-binding pocket between the α/γ or α/δ nAChR subunits (Chen et al, 2006). It causes a postsynaptic block at the NMJ nAChRs by preventing the binding of acetylcholine to its receptor. Long neurotoxins like Cobratoxin also block neuronal α7 nAChRs (Hue et al, 2007), but it is unclear how effectively the long neurotoxin can reach the central nervous system (CNS).

Toxicity

The lethal dosis (LD₅₀) of Cobratoxin in mice is 4 µg/kg (Lipps, 2001).

Treatment

Researchers are trying to develop a vaccine against the toxin by using a replicant-deficient adenovirus containing mutated cobratoxin (Pergolizzi et al, 2005).

References

Yang, C.C. (1965), " ", J. Biol Chem 240: 1616-8.

Zeng, D. & Hawrot, E. (2002), " ", J. Biol Chem 277 (40): 37439-45..

Konstantakaki, M.; Changeux, J.P & Taly, A (2007), " ", Biochem Biophys Res Commun 359 (3): 413-8.

Servent, D. & et al (2000), " ", Eur J Pharmacol 393 (1-3): 197-204.

Chen, Z.X & et al (2006), " ", Acta Pharmacol Sin 27 (4): 402-8.

Hue, B. & et al (2007), " ", Invert Neurosci 7 (3): 173-8.

Lipps, B.V. (2001), " ", J Nat Toxins 10 (1): 27-32.

Pergolizzi, R.G & et al (2005), " ", Gene Ther 16 (3): 292-8.