Charybdotoxin

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

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]

Contents

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]

Related Research Articles

<span class="mw-page-title-main">Deathstalker</span> Species of arachnid

The deathstalker is a species of scorpion, a member of the family Buthidae. It is also known as the Palestine yellow scorpion, Omdurman scorpion, and Naqab desert scorpion, as well as by many other colloquial names, which generally originate from the commercial captive trade of the animal. To eliminate confusion, especially important with potentially dangerous species, the scientific name is normally used to refer to them. The name Leiurus quinquestriatus roughly translates into English as "five-striped smooth-tail". In 2014, the subspecies L. q. hebraeus was separated from it and elevated to its own species Leiurus hebraeus. Other species of the genus Leiurus are also often referred to as "deathstalkers". Leiurus quinquestriatus is yellow, and 30–77 millimetres (1.2–3.0 in) long, with an average of 58 mm (2.3 in).

<span class="mw-page-title-main">Chlorotoxin</span> Chemical compound

Chlorotoxin is a 36-amino acid peptide found in the venom of the deathstalker scorpion which blocks small-conductance chloride channels. The fact that chlorotoxin binds preferentially to glioma cells has allowed the development of methods for the treatment and diagnosis of several types of cancer.

<span class="mw-page-title-main">Slotoxin</span> Chemical compound

Slotoxin is a peptide from Centruroides noxius Hoffmann scorpion venom. It belongs to the short scorpion toxin superfamily.

<span class="mw-page-title-main">Scyllatoxin</span> Scorpion toxin

Scyllatoxin (also leiurotoxin I) is a toxin, from the scorpion Leiurus quinquestriatus hebraeus, which blocks small-conductance Ca2+-activated K+ channels. It is named after Scylla, a sea monster from Greek mythology. Charybdotoxin is also found in the venom from the same species of scorpion, and is named after the sea monster Charybdis. In Greek mythology, Scylla and Charybdis lived on rocks on opposing sides of a narrow strait of water.

<span class="mw-page-title-main">Margatoxin</span>

Margatoxin (MgTX) is a peptide that selectively inhibits Kv1.3 voltage-dependent potassium channels. It is found in the venom of Centruroides margaritatus, also known as the Central American Bark Scorpion. Margatoxin was first discovered in 1993. It was purified from scorpion venom and its amino acid sequence was determined.

<span class="mw-page-title-main">Agitoxin</span>

Agitoxin is a toxin found in the venom of the scorpion Leiurus quinquestriatus hebraeus. Other toxins found in this species include charybdotoxin (CTX). CTX is a close homologue of Agitoxin.

Iberiotoxin (IbTX) is an ion channel toxin purified from the Eastern Indian red scorpion Hottentotta tamulus. Iberiotoxin selectively inhibits the current through large-conductance calcium-activated potassium channels.

<span class="mw-page-title-main">Scorpion toxin</span>

Scorpion toxins are proteins found in the venom of scorpions. Their toxic effect may be mammal- or insect-specific and acts by binding with varying degrees of specificity to members of the Voltage-gated ion channel superfamily; specifically, voltage-gated sodium channels, voltage-gated potassium channels, and Transient Receptor Potential (TRP) channels. The result of this action is to activate or inhibit the action of these channels in the nervous and cardiac organ systems. For instance, α-scorpion toxins MeuNaTxα-12 and MeuNaTxα-13 from Mesobuthus eupeus are neurotoxins that target voltage-gated Na+ channels (Navs), inhibiting fast inactivation. In vivo assays of MeuNaTxα-12 and MeuNaTxα-13 effects on mammalian and insect Navs show differential potency. These recombinants exhibit their preferential affinity for mammalian and insect Na+ channels at the α-like toxins' active site, site 3, in order to inactivate the cell membrane depolarization faster[6]. The varying sensitivity of different Navs to MeuNaTxα-12 and MeuNaTxα-13 may be dependent on the substitution of a conserved Valine residue for a Phenylalanine residue at position 1630 of the LD4:S3-S4 subunit or due to various changes in residues in the LD4:S5-S6 subunit of the Navs. Ultimately, these actions can serve the purpose of warding off predators by causing pain or to subdue predators.

<span class="mw-page-title-main">Potassium channel blocker</span> Several medications that disrupt movement of K+ ions

Potassium channel blockers are agents which interfere with conduction through potassium channels.

<span class="mw-page-title-main">Lq2</span>

Lq2 is a component of the venom of the scorpion Leiurus quinquestriatus. It blocks various potassium channels, among others the inward-rectifier potassium ion channel ROMK1.

<span class="mw-page-title-main">Pandinotoxin</span> Chemical compound

Pandinotoxins are toxins from the venom of the emperor scorpion Pandinus imperator. They are selective blockers of voltage-gated potassium channels

<span class="mw-page-title-main">Pandinus imperator (Pi3) toxin</span>

Pi3 toxin is a purified peptide derivative of the Pandinus imperator scorpion venom. It is a potent blocker of voltage-gated potassium channel, Kv1.3 and is closely related to another peptide found in the venom, Pi2.

Tamulotoxin is a venomous neurotoxin from the Indian Red Scorpion.

HgeTx1 (systematic name: α-KTx 6.14) is a toxin produced by the Mexican scorpion Hoffmanihadrurus gertschi that is a reversible blocker of the Shaker B K+-channel, a type of voltage-gated potassium channels.

Pi4 is a short toxin from the scorpion Pandinus imperator that blocks specific potassium channels.

<span class="mw-page-title-main">Noxiustoxin</span> Toxin from the venom of the scorpion Centruroides noxius

Noxiustoxin (NTX) is a toxin from the venom of the Mexican scorpion Centruroides noxius Hoffmann which block voltage-dependent potassium channels and calcium-activated potassium channels.

Pi5 toxin is a peptide found in the venom of the African emperor scorpion Pandinus imperator. Pi5 inhibits human Kv1.2 and Kv1.3 channels as well as Drosophila Shaker B potassium channels.

<i>Leiurus abdullahbayrami</i> Species of scorpion

Leiurus abdullahbayrami is a species of scorpion in the family Buthidae. Its venom is highly toxic to humans, but can be used in medical development.

Humans use scorpions both practically, for medicine, food, and pets, and symbolically, whether as gods, to ward off harm, or to associate a product or business with the evident power of the small but deadly animal.


N58A is a peptide depressant β-neurotoxin found in the venom of certain East Asian scorpions. The toxin affects voltage-gated sodium channels, specifically Nav1.8 & Nav1.9 channels.

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. 1 2 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.
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