A scorpion toxin or Multiple sclerosis drug

  • سال انتشار: 1398
  • محل انتشار: پانزدهمین همایش سراسری سم شناسی ایران
  • کد COI اختصاصی: TOXICOLOGY15_068
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 465
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نویسندگان

Masoumeh Baradaran

Assistant professor, Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

چکیده

Scorpion venom is an important source of bioactive molecules. Toxins and other venom peptides have been introduced as new targets for drug design. So some new studies have been conducted to identification of scorpion venom peptides in more details. Here the cDNA constructed from extracted total RNA from the Iranian scorpion Mesobuthus eupeus (Buthidae family) venom was inserted to special vectors and transformed to chemical competent E. coli as host. Clones with positive insert identified as M. eupeus cDNA library. We found the full length cDNA sequence of a potassium channel toxin (named meuK1.16) in transcriptome analysis of M. eupeus venom gland. We obtained amino acid sequences of meuK1.16 and modeled its 3D structural model using homology modeling. The model structure is further refined by energy minimization and molecular dynamics methods. The meuK1.16 structure is highlighted by an CS-α/β folding, an alpha helix connected to an anti-parallel beta sheet by three disulfide bridges. meuK1.16 has been described as a pore blocker. Alanine scanning and bioinformatics analysis performed on meuK1.16 has shown that two residues, i.e. Tyr36 and Lys27 are crucial for channel inhibition. These residues are thought to form a dyad, as already described for potassium channel blockers. It suggests that meuK1.16 after interaction with potassium channel through aromatic amino acids(Tyr36) block the channel by inserting the lysine amino acid side chain into the pore of the channel. Potassium channel blockers are proper candidates in drug design for treatment of autoimmune disease like Multiple sclerosis. Our data will be helpful for more investigation on functional action and specialized role of meuK1.16 in Multiple sclerosis drug development.

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