|Alt. symbols||ChTX-Lq1, ChTx-a|
|PDB||2crd More structures|
Charybdotoxin (CTX) is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus (Deathstalker) that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous system. It is a close homologue of agitoxin and both toxins come from Leiurus quinquestriatus hebraeus.
Scorpions such as the deathstalker paralyze their prey by injecting a potent mix of peptide toxins. Charybdotoxin, a 37 amino acid, 4 kDa neurotoxin with the molecular formula C176H277N57O55S7, is one of the peptide toxins that can be extracted from the venom of the scorpion. Its structure is very similar to that of margatoxin. Charybdotoxin contains three disulfide bridges.
Mode of action
Charybdotoxin occludes the pore of calcium-activated voltage-gated Shaker K+ channels by binding to one of four independent, overlapping binding sites. It binds both to the open and the closed states. In addition, the block is enhanced as the ionic strength is lowered. This block occurs as the Asn 30 on the CTX interacts with the Asp 381 on the K+ channel. The blockade of K+ channels by the charybdotoxin peptide causes neuronal hyperexcitability. Mutations of the Lys31Gln and the Asn30Gln had the effect of lessening the CTX block of the pore on the Shaker channel.
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 period (10 vs 16–42 hours).
- Ben-Tal N, Honig B, Miller C, McLaughlin S (October 1997). "Electrostatic binding of proteins to membranes. Theoretical predictions and experimental results with charybdotoxin and phospholipid vesicles". Biophys. J. 73 (4): 1717–27. PMC . PMID 9336168. doi:10.1016/S0006-3495(97)78203-1.
- Laurent F, Michel A, Bonnet PA, Chapat JP, Boucard M (March 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. PMC . PMID 7682131. doi:10.1111/j.1476-5381.1993.tb12851.x.
- Tenenholz TC, Rogowski RS, Collins JH, Blaustein MP, Weber DJ (1997). "Solution Structure for Pandinus Toxin K-R (PiTX-KR), a Selective Blocker of A-Type Potassium Channels". Biochemistry. 11;36(10): 2763–71. doi:10.1021/bI9628432.
- Purves D, Augustine GJ, Fitzpatrick D, Hall WC, Lamantia AS, McNamara JO, Williams SM. Neuroscience, p82.
- Avdonin V, Nolan B, Sabatier JM, De Waard M, Hoshi T (August 2000). "Mechanisms of maurotoxin action on Shaker potassium channels". Biophys. J. 79 (2): 776–87. PMC . PMID 10920011. doi:10.1016/S0006-3495(00)76335-1.
- Thompson J, Begenisich T (May 2000). "Electrostatic interaction between charybdotoxin and a tetrameric mutant of Shaker K(+) channels". Biophys. J. 78 (5): 2382–91. PMC . PMID 10777734. doi:10.1016/S0006-3495(00)76782-8.
- Naranjo D, Miller C (January 1996). "A strongly interacting pair of residues on the contact surface of charybdotoxin and a Shaker K+ channel". Neuron. 16 (1): 123–30. PMID 8562075. doi:10.1016/S0896-6273(00)80029-X.
- MacKinnon R, Reinhart PH, White MM (December 1988). "Charybdotoxin block of Shaker K+ channels suggests that different types of K+ channels share common structural features". Neuron. 1 (10): 997–1001. PMID 2483094. doi:10.1016/0896-6273(88)90156-0.
- Gao YD, Garcia ML (August 2003). "Interaction of agitoxin2, charybdotoxin, and iberiotoxin with potassium channels: selectivity between voltage-gated and Maxi-K channels". Proteins. 52 (2): 146–54. PMID 12833539. doi:10.1002/prot.10341.
- Natu VS, Murthy RK, Deodhar KP (April 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. PMID 16944610.