The amino acid sequence of Bestoxin
N - Ala - Asp - Val - Pro - Gly - Asn - Tyr - Pro - Leu - Asp - Lys - Asp - Gly - Asn - Thr - Tyr - Thr - Cys - Leu - Glu - Leu - Gly - Glu - Asn - Lys - Asp - Cys - Gln - Lys - Val - Cys - Lys - Leu - His - Gly - Val - Gln - Tyr - Gly - Tyr - Cys - Tyr - Ala - Phe - Ser - Cys - Trp - Cys - Lys - Glu - Tyr - Leu - Asp - Asp - Lys - Asp - Ser - Val - OH

Bestoxin is a neurotoxin

Neurotoxin

A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...

 from the venom

Venom

Venom is the general term referring to any variety of toxins used by certain types of animals that inject it into their victims by the means of a bite or a sting...

 of the South African spitting (or fattail) scorpion Parabuthus transvaalicus

Parabuthus transvaalicus

Parabuthus transvaalicus is a species of scorpion from southern Africa. It is also known as "Dark Scorpion".-Description:P. transvaalicus grows to a length of , and is dark brown or black in colour. Its pincers are thin, but its tail is thickened, with the sting segment being as wide as the rest of...

. Most likely, it targets sodium channel function, thus promoting spontaneous and repetitive neuronal firing. Following injection into mice, it causes non-lethal writhing behaviour.

Source

Bestoxin is one of the many components that can be isolated from the venom of the South African spitting scorpion (pictured right). Other peptide toxins also found in the venom include: dortoxin

Dortoxin

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.-Source:...

, birtoxin

Birtoxin

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.-Source:...

, and altitoxin

Altitoxin

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

. Together with birtoxin, dorotoxin, altitoxin and ikitoxin

Ikitoxin

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.-Source:...

, this mammal-specific ion channel

Ion channel

Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

 toxin is a member of the birtoxin polypeptide family. These birtoxin-like polypeptides contribute significantly to the venom’s toxicity

Toxicity

Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...

, since they constitute at least 30% of the peptides in the venom of this scorpion.

Chemistry

Although the birtoxin-like polypeptides, including bestoxin, are 58 amino acids long and have only three disulfide bridges, they resemble long chain neurotoxins, which typically have a length of 60–70 amino acids and four disulfide bridges. Bestoxin, as most of the known scorpion toxins, has α-helixes that are lined up with basic amino acid residues. Furthermore, bestoxin has localized positively and negatively charged surfaces, a unique property of the birtoxin polypeptide family.

Target & mode of action

Based on its resemblance to long chain β-neurotoxins, bestoxin most likely binds to neurotoxin receptor site 4 of the sodium channel. Binding of long chain β-neurotoxins is voltage-independent, and results in a shift of the voltage-activation curve towards more negative potentials, inducing abnormal sodium channel permeability and promoting spontaneous and repetitive firing.

Toxicity

Mice injected with bestoxin show intense writhing. This abnormal behavior is characterized by twisting of the neck, followed by the body, and making a full turn around the body axis. The intensity of this behavior increases over time and the mice start to spin around. After approximately 24 hours the amount of writhing decreases and the twisting behavior gradually slows down to one turn per two seconds. Furthermore, there is no lethality observed. The dosage that produces a desired effect in 99% of the test population, or ED99, of bestoxin is 100 ng of peptide per 20 g mouse bodyweight. No data is available on the effect of bestoxin in humans or primates.

Treatment

Bestoxin is one of the many neurotoxic peptidic components in the venom of the South African spitting scorpion. The birtoxin-like peptides share an N-terminus of eighteen amino acid residues. Neutralization of this domain results in a decrease of toxicity of the venom. Mass spectrometry

Mass spectrometry

Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...

 and western blotting confirmed that these neurotoxins react with polyclonal antibodies and it is proposed that polyclonal antibodies will neutralize the N-terminus domain and finally the venom in a dose dependent manner. Moreover, previous work has proven that this polyclonal antibody approach is an effective strategy for antivenom production.