Charybdotoxin

Charybdotoxin (ChTX) is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus (deathstalker) that blocks calcium-activated potassium channels.^[2] This blockade causes hyperexcitability of the nervous system. It is a close homologue of agitoxin and both toxins come from Leiurus quinquestriatus hebraeus. It is named after Charybdis, a sea monster from Greek myth.^[3]

Charybdotoxin
Refined model of Charybdotoxin. PDB 2crd.[1]
Identifiers
Organism	Leiurus quinquestriatus hebraeus
Symbol	ChTX
Alt. symbols	ChTX-Lq1, ChTx-a
CAS number	95751-30-7
PDB	2crd More structures
UniProt	P13487
Search for Structures Swiss-model Domains InterPro

Chemical properties

Family

The Charybdotoxin family of scorpion toxins is a group of small peptides that has many family members, such as the pandinotoxin, derived from the venom of scorpion Pandinus imperator.^[4]

Structure

Scorpions such as the deathstalker paralyze their prey by injecting a potent mix of peptide toxins.^[5] 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.^[6]

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.^[7][8] It binds both to the open and the closed states. In addition, the block is enhanced as the ionic strength is lowered.^[9] This block occurs as the Asn ³⁰ on the CTX interacts with the Asp ³⁸¹ on the K+ channel.^[10] 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.^[10]

Treatment

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).^[11]

References

1. 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. Bibcode:1997BpJ....73.1717B. doi:10.1016/S0006-3495(97)78203-1. PMC 1181073. PMID 9336168.
2. 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. doi:10.1111/j.1476-5381.1993.tb12851.x. PMC 1908044. PMID 7682131.
3. Senning A (2006-10-30). Elsevier's Dictionary of Chemoetymology: The Whys and Whences of Chemical Nomenclature and Terminology. Elsevier. ISBN 978-0-08-048881-3.
4. 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. 36 (10): 2763–71. doi:10.1021/bI9628432. PMID 9062103.
5. Purves D, Augustine GJ, Fitzpatrick D, Hall WC, Lamantia AS, McNamara JO, Williams SM. Neuroscience, p82.
6. 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. Bibcode:2000BpJ....79..776A. doi:10.1016/S0006-3495(00)76335-1. PMC 1300977. PMID 10920011.
7. Thompson J, Begenisich T (May 2000). "Electrostatic interaction between charybdotoxin and a tetrameric mutant of Shaker K(+) channels". Biophys. J. 78 (5): 2382–91. Bibcode:2000BpJ....78.2382T. doi:10.1016/S0006-3495(00)76782-8. PMC 1300827. PMID 10777734.
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. doi:10.1016/S0896-6273(00)80029-X. PMID 8562075. S2CID 16794677.
9. 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. doi:10.1016/0896-6273(88)90156-0. PMID 2483094. S2CID 44466070.
10. 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. doi:10.1002/prot.10341. PMID 12833539. S2CID 7136604.
11. 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.