Modeling and Molecular dynamic simulations of two potent Kv blocker in the M. eupeus venom gland

Scorpion venom is an important source for biologically active components with pharmacological potentials. Potassium channels blockers, one group of scorpion venom toxins can be good candidate for treatment of different disease, including cardiac and neuronal. The transcriptomic approach of mesobuthus eupeus venom gland, known as the most frequent Iranian scorpions, revealed the repertoire of possible peptides present in the venom, includingmany toxins. Two of them were named meuK1.16 and meuTx22. The mature peptide of meuK1.16 and meuTx22 is 37a and 32 aa, respectively. According to similarity with the protein database, these peptides are two potent potassium channel blocker; and are belong to α-KTx subfamily. The three-dimensional structure of meuK1.16 and meuTx22 was obtained by computational modeling and refined by molecular dynamic simulations. Furthermore,using molecular assessment of similar peptides a function prediction was made for these two potent potassium channel toxins in which the amino acid residues that could be involved in the potassium channel/toxin interactions was proposed. A CSα/β (cysteine-stabilized α-helicaland β-sheet) fold was found for the 3-D structure of meuK1.6, while structure of meuTX22 was composed of a modified CSα/β fold. functional analysis suggests a key role for residues Lys27 and Tyr36 of meuK1.6; and Lys23 and Tyr26 of meuTx22 in the interaction and blockage ofthe Kv channels (functional dyad).

Keywords:

Mesobuthus eupeus , venom components , potent Kv blocker , modeling