Bestoxin is a neurotoxin from the

venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a st ...

of the South African spitting (or fattail) scorpion '' Parabuthus transvaalicus''. Most likely, it targets

sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the chann ...

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

Sources

Bestoxin is one of the many components that can be isolated from the venom of the South African spitting scorpion. Other peptide toxins also found in the venom include dortoxin, birtoxin, and altitoxin. Together with birtoxin, dorotoxin, altitoxin and ikitoxin, this mammal-specific ion channel toxin is a member of the birtoxin polypeptide family. These birtoxin-like polypeptides contribute significantly to the venom's

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...

, 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 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 ...

, 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.https://www.uniprot.org/uniprot/P0C1B6 - Bestoxin - Parabuthus transvaalicus (South African fattail scorpion)

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 and

western blotting The western blot (sometimes called the protein immunoblot), or western blotting, is a widely used analytical technique in molecular biology and immunogenetics to detect specific proteins in a sample of tissue homogenate or extract. Besides detect ...

confirmed that these neurotoxins react with

polyclonal antibodies Polyclonal antibodies (pAbs) are antibodies that are secreted by different B cell lineages within the body (whereas monoclonal antibodies come from a single cell lineage). They are a collection of immunoglobulin molecules that react against ...

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.

References

{{toxins Neurotoxins Ion channel toxins Scorpion toxins