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- Title
Expression, Purification and Docking Studies on IMe-AGAP, the First Antitumor-analgesic Like Peptide from Iranian Scorpion Mesobuthus eupeus.
- Authors
Dehghan, Zeinab; Ayat, Hoda; Ahadi, Ali Mohammad
- Abstract
Scorpion venom contains different toxins with multiple biological functions. IMe-AGAP is the first Analgesic-Antitumor like Peptide (AGAP) isolated from Iranian scorpion Mesobuthus eupeus. This peptide is similar to AGAP toxin with high analgesic activity, extracted from Chinese scorpion and inhibits NaV1.8 and NaV1.9 voltage-gated sodium channels involved in the pain pathway. In this study, IMe-AGAP was cloned in a prokaryotic expression vector; expression of toxin in Escherichia coli (E. coli) was assayed and then purified. In in-silico studies, peptide sequence was compared with other scorpion analgesic toxins. The structures of IMe-AGAP and sodium channels were modeled using homology modeling. Structural evaluation and stereo-chemical analysis of modeled structures were performed using RAMPAGE web server Ramachandran plots. Hex Server was used to investigate the interactions between IMe- AGAP and S3-S4 and also S5-S6 segments of NaV1.8 and NaV1.9. Binding energies calculation was used for evaluation of protein docking. Soluble expression of IMe-AGAP in bacteria was investigated by SDS-PAGE analysis. Pure recombinant protein was obtained by Ni-NTA affinity chromatography. The results of three-dimensional structure prediction showed βαββ topology for the toxin that is similar to the conserved structure of α-toxins. Comparison analysis between IMe-AGAP and AGAP toxins exhibited high similarity in homology modeling. Docking analysis demonstrated that IMe-AGAP can interact with NaV1.8 and NaV1.9 domains involved in pain. According to the results of homology studies and docking, IMe-AGAP might be a novel potential drug for pain treatment.
- Subjects
CONOTOXINS; ESCHERICHIA coli toxins; SCORPIONS; SIGNAL recognition particle receptor; SCORPION venom; RECOMBINANT proteins; SODIUM channels
- Publication
Iranian Journal of Pharmaceutical Research, 2020, Vol 19, Issue 3, p206
- ISSN
1735-0328
- Publication type
Article
- DOI
10.22037/ijpr.2019.15339.13028