Charybdotoxin (CTX) is a 37

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature nerv ...

from the venom of the

scorpion Scorpions are predatory arachnids of the order Scorpiones. They have eight legs, and are easily recognized by a pair of grasping pincers and a narrow, segmented tail, often carried in a characteristic forward curve over the back and always en ...

'' Leiurus quinquestriatus hebraeus'' (''deathstalker'') that blocks calcium-activated

potassium channels Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cel ...

. 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 Charybdis (; grc, Χάρυβδις, Khárybdis, ; la, Charybdis, ) is a sea monster in Greek mythology. She, with the sea monster Scylla, appears as a challenge to epic characters such as Odysseus, Jason, and Aeneas. Scholarship locates her in ...

, a sea monster from Greek myth.

Chemical properties

Family

The Charybdotoxin family of scorpion toxins is a group of small peptides that has many family members, such as the

pandinotoxin Pandinotoxins are toxins from the venom of the emperor scorpion ''Pandinus imperator''. They are selective blockers of voltage-gated potassium channels Sources The source for the pandinotoxins is the venom of the scorpion ''Pandinus imperato ...

, derived from the venom of scorpion

Pandinus imperator The emperor scorpion, ''Pandinus imperator'', is a species of scorpion native to rainforests and savannas in West Africa. It is one of the largest scorpions in the world and lives for 6–8 years. Its body is black, but like other scorpions it ...

Structure

Scorpions such as the

deathstalker The deathstalker (''Leiurus quinquestriatus'') is a species of scorpion, a member of the family Buthidae. It is also known as the Palestine yellow scorpion, Omdurman scorpion, Naqab desert scorpion and by many other colloquial names, which gene ...

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 bridge In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

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 Alpha (uppercase , lowercase ; grc, ἄλφα, ''álpha'', or ell, άλφα, álfa) is the first letter of the Greek alphabet. In the system of Greek numerals, it has a value of one. Alpha is derived from the Phoenician letter aleph , whi ...

it has a relatively short recovery period (10 vs 16–42 hours).

References

{{Potassium channel blockers Neurotoxins Ion channel toxins Scorpion toxins Potassium channel blockers