Charybdotoxin Explained

Charybdotoxin
Width:	218px
Organism:	Leiurus quinquestriatus hebraeus
Symbol:	ChTX
Altsymbols:	ChTX-Lq1, ChTx-a
Cas Number:	95751-30-7
Pdb:	2crd
Pdb Supplemental:	More structures
Uniprot:	P13487

Charybdotoxin (ChTX) is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus (deathstalker) that blocks calcium-activated potassium channels.^[1] 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.^[2]

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.^[3]

Structure

Scorpions such as the deathstalker paralyze their prey by injecting a potent mix of peptide toxins.^[4] 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.^[5]

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.^{[6] [7]} It binds both to the open and the closed states. In addition, the block is enhanced as the ionic strength is lowered.^[8] This block occurs as the Asn ³⁰ on the CTX interacts with the Asp ³⁸¹ on the K+ channel.^[9] 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.^[9]

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).^[10]

Notes and References

1. Laurent F, Michel A, Bonnet PA, Chapat JP, Boucard M . 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 . March 1993 . 7682131 . 1908044 . 10.1111/j.1476-5381.1993.tb12851.x.
2. Book: Senning, Alexander . vanc . Elsevier's Dictionary of Chemoetymology: The Whys and Whences of Chemical Nomenclature and Terminology . 2006-10-30 . Elsevier . 978-0-08-048881-3 .
3. Tenenholz TC, Rogowski RS, Collins JH, Blaustein MP, Weber DJ . Solution Structure for Pandinus Toxin K-R (PiTX-KR), a Selective Blocker of A-Type Potassium Channels . Biochemistry . 36. 2763–71. 1997 . 10 . 10.1021/bI9628432 . 9062103.
4. Purves D, Augustine GJ, Fitzpatrick D, Hall WC, Lamantia AS, McNamara JO, Williams SM. Neuroscience, p82.
5. Avdonin V, Nolan B, Sabatier JM, De Waard M, Hoshi T . Mechanisms of maurotoxin action on Shaker potassium channels . Biophys. J. . 79 . 2 . 776–87 . August 2000 . 10920011 . 1300977 . 10.1016/S0006-3495(00)76335-1. 2000BpJ....79..776A .
6. Thompson J, Begenisich T . Electrostatic interaction between charybdotoxin and a tetrameric mutant of Shaker K(+) channels . Biophys. J. . 78 . 5 . 2382–91 . May 2000 . 10777734 . 1300827 . 10.1016/S0006-3495(00)76782-8 . 2000BpJ....78.2382T .
7. Naranjo D, Miller C . A strongly interacting pair of residues on the contact surface of charybdotoxin and a Shaker K+ channel . Neuron . 16 . 1 . 123–30 . January 1996 . 8562075 . 10.1016/S0896-6273(00)80029-X . 16794677 . free .
8. MacKinnon R, Reinhart PH, White MM . Charybdotoxin block of Shaker K+ channels suggests that different types of K⁺ channels share common structural features . Neuron . 1 . 10 . 997–1001 . December 1988 . 2483094 . 10.1016/0896-6273(88)90156-0 . 44466070 .
9. Gao YD, Garcia ML . Interaction of agitoxin2, charybdotoxin, and iberiotoxin with potassium channels: selectivity between voltage-gated and Maxi-K channels . Proteins . 52 . 2 . 146–54 . August 2003 . 12833539 . 10.1002/prot.10341 . 7136604 .
10. Natu VS, Murthy RK, Deodhar KP . 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 . April 2006 . 16944610 .