Birtoxin

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Birtoxin
CategoryIon channel toxin, Neurotoxin
Species Parabuthus transvaalicus [1]
Target voltage-gated sodium channel [1]
Symptoms tachypnea, convulsions, tremors, death
Taxonomic ID 170972 [1]
Sequence length 58 AA [1]

Birtoxin is a neurotoxin from the venom of the South African Spitting scorpion (Parabuthus transvaalicus). By changing sodium channel activation, the toxin promotes spontaneous and repetitive firing much like pyrethroid insecticides do

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South African spitting scorpion (Parabuthus transvaalicus) Parabuthus transvaalicus (male).jpg
South African spitting scorpion (Parabuthus transvaalicus)

Birtoxin was isolated from the venom of the South African Spitting scorpion. [1] It is a peptide that is moderately toxic but very abundant in the venom. [1] Other peptide toxins found in the venom include: dortoxin, a lethal peptide; bestoxin, which causes writhing in mice; and altitoxin, a highly depressant peptide. [2]

Chemistry

Generally, peptide neurotoxins can be divided into two major families, the ‘long chain neurotoxins’ (LCN) with 60- to 70-residue range and known to contain eight cysteine residues; and the ‘short chain neurotoxins’ (SCN) with 30 to 40 peptides with six or eight cysteine residues. Birtoxin, together with other birtoxin-like peptides including bestoxin, is 58 amino-acid residues long, close to the ‘long chain’ family but with six cysteine residues. Birtoxin is reticulated by three disulfide bridges, instead of four, compared to other LCNs . [3] Therefore, it is considered to be the evolutionary link between ‘long chain’- and ‘short chain’- families. [4] [5] [6] [7]

Mode of action

Birtoxin affects the gating mechanism of sodium channels by binding to neurotoxin receptor site 4 of the channel, resulting in the lowering of the voltage threshold of the channel and a reduction in the current amplitude. Due to the change in the activation the sodium channel will open at smaller depolarisations. This causes increased excitability, which leads to symptoms such as convulsions, continuous urination, tremors and tachypnea (faster breathing). [1] [8]

Toxicity

Birtoxin only affects mammals. No effect is found on reptiles, insects or fish. In experiments performed on mice, symptoms such as convulsions, continuous urination, tremors and tachypnea occurred 10 minutes after injection and increased during 30 minutes. An injection of 1 μg of birtoxin resulted in severe neurotoxic effects for 24 hours, but this dose is not lethal to mice. LD99 in mice is achieved at 2 μg. [1]

An antibody against the N-terminus of the birtoxin protein structure has been shown to neutralize the venom of the South African spitting scorpion, and such antibodies may be useful clinically to treat envenomation. [9]

Related Research Articles

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Delta atracotoxin is a low-molecular-weight neurotoxic polypeptide found in the venom of the Sydney funnel-web spider.

Tityustoxin is a toxin found in the venom of scorpions from the subfamily Tityinae. By binding to voltage-dependent sodium ion channels and potassium channels, they cause sialorrhea, lacrimation and rhinorrhea.

Bestoxin is a neurotoxin from the venom of the South African spitting scorpion Parabuthus transvaalicus. Most likely, it targets sodium channel function, thus promoting spontaneous and repetitive neuronal firing. Following injection into mice, it causes non-lethal writhing behaviour.

BmKAEP is a neurotoxin from the venom of the Manchurian scorpion (Mesobuthus martensii). It is a β-toxin, which shift the activation voltage of sodium channels towards more negative potentials.

Altitoxin is a neurotoxin found in the South African scorpion Parabuthus transvaalicus. Injection of altitoxin in mice leads to akinesia, depression and death.

Dortoxin is a lethal peptide toxin which is secreted by the South African spitting scorpion Parabuthus transvaalicus. Injection of pure dortoxin in mice leads to hyperactivity that lasts until death.

Ikitoxin is a neurotoxin from the venom of the South African Spitting scorpion that targets voltage-sensitive sodium channels. It causes unprovoked jumps in mice following intracerebroventricular injections.

<i>delta</i>-Palutoxin

delta-Palutoxins (δ-palutoxins) consist of a homologous group of four insect-specific toxins from the venom of the spider Pireneitega luctuosa. They show a high toxicity against Spodoptera litura larvae by inhibiting sodium channels, leading to strong paralytic activity and eventually to the death of the insect.

Oxotoxins, or oxytoxins, are a group of neurotoxins present in the venom of lynx spiders belonging to the genus Oxyopes, hence the name oxytoxin. They are disulfide-rich peptides. Only two types are so far reported from two different species, the larger oxytoxin 1 (OxyTx1) from Oxyopes kitabensis, and the smaller oxytoxin 2 (OxyTx2) from Oxyopes lineatus. OxyTx1, the first known oxytoxin, was discovered in 2002. It was found to enhance the lethal efficacy of the spider venom by acting together with oxyopinins. It is composed of 69 amino acid residue, which are cross-linked by five disulfide bridges. It is a large peptide having a molecular mass of 8059.2 Da; but shows the size of 9,109.4 Da due to the presence of disulfide bridges. It is a potent insecticide, but non-toxic to mice up to 1 μg/20-g mouse. It acts synergistically with oxyopinins of the same venom to increase the insecticidal effect.

Tamulotoxin is a venomous neurotoxin from the Indian Red Scorpion.

Cll1 Scorpion protein

Toxin Cll1 is a toxin from the venom of the Mexican scorpion Centruroides limpidus limpidus, which changes the activation threshold of sodium channels by binding to neurotoxin binding site 4, resulting in increased excitability.

Centruroides suffusus suffusus toxin II (CssII) is a scorpion β-toxin from the venom of the scorpion Centruroides suffusus suffusus. CssII primarily affects voltage-gated sodium channels by causing a hyperpolarizing shift of voltage dependence, a reduction in peak transient current, and the occurrence of resurgent currents.

Spinoxin is a 34-residue peptide neurotoxin isolated from the venom of the Malaysian black scorpion Heterometrus spinifer. It is part of the α-KTx6 subfamily and exerts its effects by inhibiting voltage-gated potassium channels, specifically Kv1.2 and Kv1.3.

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.

Noxiustoxin

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.

Beta-mammal toxin Cn2, also known as Cn2 toxin, is a single chain β-scorpion neurotoxic peptide and the primary toxin in the venom of the Centruroides noxius Hoffmann scorpion. The toxin specifically targets mammalian Nav1.6 voltage-gated sodium channels (VGSC).

Beta-toxin Cll2, shortened to Cll2, is a toxin in the venom of the Mexican Scorpion species Centruroides limpidus limpidus. The toxin belongs to the β-class family of sodium channel-inhibiting scorpion toxins. It affects voltage-dependent activation, conductance and resurgent currents of voltage gated sodium channels by binding to site 4.

LmαTX5 is an α-scorpion toxin which inhibits the fast inactivation of voltage-gated sodium channels. It has been identified through transcriptome analysis of the venom gland of Lychas mucronatus, also known as the Chinese swimming scorpion – a scorpion species which is widely distributed in Southeast Asia.

Versutoxin

Delta hexatoxin Hv1 is a neurotoxic component found in the venom of the Australian funnel web spider.

References

  1. 1 2 3 4 5 6 7 8 Inceoglu, B.; Lango, J.; Wu, J.; Hawkins, P.; Southern, J.; Hammock, B.D. (2001). "Isolation and characterization of a novel type of neurotoxic peptide from the venom of the South African scorpion Parabuthus transvaalicus (Buthidae)". European Journal of Biochemistry. 268 (20): 5407–5413. doi: 10.1046/j.0014-2956.2001.02479.x . PMID   11606203.
  2. Inceoglu, B; J Lango; I Pessah; B Hammock (2005). "Three structurally related, highly potent, peptides from the venom of possess divergent biological activity". Toxicon. 45 (6): 727–733. doi:10.1016/j.toxicon.2005.01.020. ISSN   0041-0101. PMID   15804521.
  3. Martin-Eauclaire, M-F; Cearda, B.; Bosmans, F.; Rossoa, J-P.; Tytgat, J.; Bougisa, P.E. (1999). "New "Birtoxin analogs" from Androctonus australis venom". Biochemical and Biophysical Research Communications. 333 (2): 524–530. doi:10.1016/j.bbrc.2005.05.148. PMID   15963953.
  4. Possani, L.D.; Becerrill, B.; Delepierre, M.; Tytgat Hammock, J. (1999). "Scorpion toxins specific for Na+-channels". European Journal of Biochemistry. 264 (2): 287–300. doi: 10.1046/j.1432-1327.1999.00625.x . PMID   10491073.
  5. Lebreton, F.; Delepierre, M.; Ramirez, A.N.; Balderas, C.; Possani, L.D. (1994). "Primary and NMR three-dimensional structure determination of a novel crustacean toxin from the venom of the scorpion Centruroides limpidus limpidus Karsch". Biochemistry. 33 (37): 11135–11149. doi:10.1021/bi00203a010. PMID   7727365.
  6. Lebreton, F.; Delepierre, M.; Ramirez, A.N.; Balderas, C.; Possani, L.D. (1994). "Purification and primary structure of low molecular mass peptides from scorpion (Buthus sindicus) venom". Comparative Biochemistry and Physiology A. 121 (4): 323–332. doi:10.1016/S1095-6433(98)10140-X. PMID   10048185.
  7. Gordon, D.; Savarin, P.; Gurevitz, M.; Zinn-Justin, S. (1998). "Functional anatomy of scorpion toxins affecting sodium channels". Toxin Reviews . 17 (2): 131–159. doi:10.3109/15569549809009247.
  8. Cestèle, S.; Catterall, W.A. (2000). "Molecular mechanisms of neurotoxin action on voltage-gated sodium channels". Biochimie. 82 (9–10): 883–892. doi:10.1016/S0300-9084(00)01174-3. PMID   11086218.
  9. Inceoglu, B; J Lango; A Rabinovich; P Whetstone; B Hammock (2006). "The neutralizing effect of a polyclonal antibody raised against the N-terminal eighteen-aminoacid residues of birtoxin towards the whole venom of Parabuthus transvaalicus". Toxicon. 47 (2): 144–149. doi:10.1016/j.toxicon.2005.08.018. ISSN   0041-0101. PMID   16356521.