Purification and Molecular Characterization of a Mammalian Neurotoxin as a Pharmaceutical Tool from the Venom of Iranian Scorpion Androctonus crassicauda.

BACKGROUND

Venom of scorpions are complex bioactive polypeptides. To gain greater insights into the structural and functional impacts of toxins from Androctonus crassicauda (Buthidae), a dangerously venomous scorpion species, its venom was isolated, purified, and characterized.

METHODS

Long chain toxin with four disulfide bonds purified by size exclusion chromatography and reversed-phase HPLC and characterized by amino acid sequencing and molecular weight determination.

RESULTS

The primary structure analysis exhibits a neurotoxin named AnCra2 with 7302.24 Da molecular weight and 64 amino acid residues that cause paralysis and lead to death in NIH mice. The LD50 of AnCra2 was determined to be 0.61±0.04 μg/mice. Phylogenetic analysis displays the toxin has 97% sequence similarity with alpha toxins reported from north African scorpions that affect voltage-gated sodium channels (VGSC), also proposed that differentiation among the scorpions of family Buthidae is affected by the geographical conditions and efficiency in evolutionary variations. AnCra2 exposed binding residues have a high affinity for receptor residues in site-3 (segment-3) of VGSC that are approved by three-dimensional structure and homology modeling.

CONCLUSION

Purified AnCra2 seems to be a new putative Alpha neurotoxin in homology with the structure of neurotoxins that act on VGSC as a pharmaceutical tool.