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Definition

Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus that blocks calcium-activated potassium channels that causes hyperexcitation of the nervous system1.

 

Discovery

CTX was first identified and partially purified from the venom of the scorpion, Leiurus quinquestriatus hebraeus in 19852.  It was found that CTX could reversibly inhibit Ca2+-activated K+ channels of mammalian skeletal muscle2.

 

Classification

CTX belongs to the charybdotoxin family of potassion channel blocking peptides3.

 

Structural Characteristics

CTX like other potassium channel blocking peptides has a characteristic fold in its peptide backbone3. It also has three disulphide bridges that hold the three stranded beta-sheet to the two to three turn alpha-helix in place3. The toxicity of CTX depends on the Lys at position 273.  Several structural analogs of CTX have been designed4.

 

Mode of action

CTX blocks potassium channels by binding to a receptor at the opening of the ion conduction pathway5.  It binds both to the open and the closed states5. In addition, the block is enhanced as the ionic strength is lowered6.

 

Functions

Scorpions such as the deathstalker paralyse their prey by injecting a potent mix of peptide toxins one of which is CTX7. Anti-scorpion venom serum (AScVS) is an effective and safe method of therapy in severe scorpion envenoming syndrome. Compared with other therapies like alpha blockers it has a relatively short recovery period8.  CTX is also a good model to study potassium channels7.

 

 

References

 

1.     Laurent F, Michel A, Bonnet PA, Chapat JP, Boucard M (1993). Evaluation of the relaxant effects of SCA40, a novel charybdotoxin-sensitive potassium channel opener, in guinea-pig isolated trachealis. Br. J. Pharmacol., 108 (3), 622–6.

2.     Miller C, Moczydlowski E, LaTorre R and Phillips M (1985). Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle. Nature (Lond), 313, 316-318.

3.     Book: Guidebook to protein toxins and their use in cell biology, Rappuoli R, Montecucco C, 143-145.

4.     Rauer H, Lanigan MD, Pennington MW, Aiyar J, Ghanshani S, Cahalan MD, Norton RS, Chandy KG (2000). Structure-guided transformation of charybdotoxin yields an analog that selectively targets Ca(2+)-activated over voltage-gated K(+) channels. J Biol Chem, 275(2), 1201-8.

5.     Naranjo D, Miller C (1996). A strongly interacting pair of residues on the contact surface of charybdotoxin and a Shaker K+ channel. Neuron, 16 (1), 123–30.

6.     MacKinnon R, Reinhart PH, White MM (1988). Charybdotoxin block of Shaker K+ channels suggests that different types of K+ channels share common structural features. Neuron, (10): 997–1001.

7.     Garcia ML, Knaus HG, Munujos P, Slaughter RS, Kaczorowski GJ (1995). Charybdotoxin and its effects on potassium channels. Am J Physiol., 269(1.1), C1-10.

8.     Natu VS, Murthy RK, Deodhar KP (2006). Efficacy of species specific anti-scorpion venom serum (AScVS) against severe, serious scorpion stings (Mesobuthus tamulus concanesis Pocock)—an experience from rural hospital in western Maharashtra. J Assoc Physicians India, 54, 283–7.

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