Ikitoxin | |
---|---|
Category | Ion channel toxin, Neurotoxin |
Species | Parabuthus transvaalicus [1] |
Target | voltage-gated sodium channel [1] |
Symptoms | Unprovoked jumps |
Sequence length | 58 AA [1] |
Ikitoxin is a neurotoxin from the venom of the South African Spitting scorpion (Parabuthus transvaalicus) that targets voltage-sensitive sodium channels. It causes unprovoked jumps in mice following intracerebroventricular injections. [1]
Ikitoxin is one of the many components that can be isolated from the venom of the South African Spitting scorpion. [1] Other peptide toxins found in the venom include birtoxin, which is moderately toxic but very abundant, dortoxin, a lethal peptide, bestoxin, which causes writhing in mice, and altitoxin, a highly depressant peptide. [2]
Ikitoxin is a member of the birtoxin family of peptide neurotoxins that target sodium channels. Although identified as a long chain neurotoxin, which usually have 64-70 residues with four disulfide bridges, ikitoxin, like birtoxin, has a smaller size (58 residues) with only three disulfide bridges. [3] Ikitoxin differs from birtoxin by a single amino acid: from glycine to glutamic acid at position 23, consistent with an apparent mass difference of 72 Da between the two peptides. [1]
Both ikitoxin and birtoxin are beta toxins, which bind to and trap the voltage sensor of the channel at side 4. The binding of ikitoxin lowers the voltage threshold of sodium channels and produce a reduction in the current amplitude. As a result of the change in their activation properties, sodium channels will open at smaller depolarizations, resulting in increased excitability. [1] [3]
Ikitoxin differs from birtoxin by only a single residue, but has a markedly reduced biological activity. In mice experiments, intracerebroventricular administration of ikitoxin induced unprovoked jumps. These jumps were observed at a concentration that was 1000-fold higher than in the case of birtoxin, and their onset was much slower. Another difference between these toxins is that birtoxin produced convulsions, tremors, increased ventilation and, subsequently, death. [1] Injection of up to 4 μg of ikitoxin in mice was not lethal. Ikitoxin seems to affect only mammals.
Ikitoxin is one of many neurotoxic polypeptide components in the venom of the South African Spitting scorpion. It has a birtoxin-like structure. Antibodies against the N-terminus of the birtoxin protein structure can neutralize the venom of the South African spitting scorpion, and such antibodies may be useful clinically to treat envenomation. [4]
Poneratoxin is a paralyzing neurotoxic peptide made by the bullet ant Paraponera clavata. It prevents inactivation of voltage gated sodium channels and therefore blocks the synaptic transmission in the central nervous system. Specifically, poneratoxin acts on voltage gated sodium channels in skeletal muscle fibers, causing paralysis, and nociceptive fibers, causing pain. It is rated as a 4 plus on the Schmidt sting pain index, the highest possible rating with that system, and its effects can cause waves of pain up to twelve hours after a single sting. Schmidt describes it as "pure, intense, brilliant pain...like walking over flaming charcoal with a three-inch nail embedded in your heel." It is additionally being studied for its uses in biological insecticides.
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.
Birtoxin is a neurotoxin from the venom of the South African Spitting scorpion. By changing sodium channel activation, the toxin promotes spontaneous and repetitive firing much like pyrethroid insecticides do
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.
Raventoxins are neurotoxins from the venom of the spider Macrothele raveni.
Huwentoxins (HWTX) are a group of neurotoxic peptides found in the venom of the Chinese bird spider Haplopelma schmidti. The species was formerly known as Haplopelma huwenum, Ornithoctonus huwena and Selenocosmia huwena. While structural similarity can be found among several of these toxins, HWTX as a group possess high functional diversity.
CSTX is a name given to a group of closely related neurotoxic peptides present in the venom of the wandering spider Cupiennius salei. There are twenty types so far described for this protein group. However, some are reclassified into cupiennins group of toxin, including CSTX-3, -4, -5, and -6, because of their chemical affinity. The first thirteen were isolated and identified in 1994 by Lucia Kuhn-Nentwig, Johann Schaller, and Wolfgang Nentwig of the Zoological Institute at the University of Bern, Switzerland. The different types are most likely the products of splicing variant of the same gene. They are all L-type calcium channel blockers, and also exhibit cytolytic activity by forming an alpha-helix across the cell membrane in mammalian neurons. They also inhibit voltage-gated calcium channels in insect neurons.
Hemitoxin (HTX; α-KTx6.15) is a 35-mer basic peptide from the venom of the Iranian scorpion Hemiscorpius lepturus, which reversibly blocks Kv1.1, Kv1.2 and Kv1.3voltage-gated K+ channels.
Butantoxin (BuTX) is a compound of the venom of three Brazilian and an Argentinean scorpion species of the genus Tityus. Butantoxin reversibly blocks the voltage-gated K+ channels Shaker B and Kv1.2, and the Ca2+-activated K+ channelsKCa 1.1 and KCa 3.1.
BotIT2 is a neurotoxin from the scorpion Buthus occitanus tunetanus, which modifies activation and slows down the deactivation of voltage gated sodium channels.
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.
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.
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).
Delta hexatoxin Hv1 is a neurotoxic component found in the venom of the Australian funnel web spider.
Ts8 is a neurotoxin present in the venom of the Brazilian yellow scorpion, Tityus serrulatus. Ts8 is a selective inhibitor of the voltage-gated potassium channel Kv4.2