Characterization, molecular modeling and phylogenetic analysis of a long mammalian neurotoxin from the venom of the Iranian scorpion Androctonus crassicauda

Abstract

Scorpion venoms are highly complex polypeptides with a wide spectrum of bioactivities. A long chain peptide with eight cysteine residues and four disulfide bonds isolated from the venom of the Iranian scorpion Androctonus crassicauda, a dangerously venomous species belongs to the Buthidae family. Toxin was purified using size exclusion and reverse phase chromatography and was characterized by molecular weight determination and amino acid sequence. The primary structure analysis shows that AnCra1 is a long peptide with 64 amino acid residues and 7255.23 Da. as molecular weight. This toxic peptide, causing severe paralysis and leading to dead. It shows highest homology with voltage-gated sodium channel alpha toxins isolated from Middle-East and North-Africa scorpions. Phylogenetic relationship of AnCra1 and other ion channel toxins from Buthidae family suggested that, separation between these families of scorpions caused by the geographical conditions led to evolutionary alterations in these venoms polypeptide sequences. Homology modeling and three-dimensional structure of AnCra1 indicated that binding residues on exposed part of the peptide have high affinity for receptor residues in Na+V ion channel, site-3. The contact surfaces characteristics and charges may be eventuate to interaction between toxin peptide and targeted channel. Molecular homology between AnCra1 with structure of Na+V neurotoxic peptides illustrated that, AnCra1 can act as novel functional putative Alpha-mammal voltage-gated sodium channel toxin.