Bestoxin
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 from the venom of the South African spitting (or fattail) 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.
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.[1] 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, since they constitute at least 30% of the peptides in the venom of this scorpion.[2]
Chemistry
Although the birtoxin-like polypeptides, including bestoxin, are 58 amino acids long and have only three
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.[3][4][5]
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.[1] 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