Charybdotoxin

Charybdotoxin
Refined model of Charybdotoxin. PDB 2crd.
Identifiers
Organism	Leiurus quinquestriatus hebraeus
Symbol	ChTX
Alt. symbols	ChTX-Lq1, ChTx-a
CAS number	95751-30-7
PDB	2crd More structures
UniProt	P13487

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.

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.

Structure

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.

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).