Folded Conformations of Maitotoxin
DOI:
https://doi.org/10.29356/jmcs.v52i1.1049Keywords:
maitotoxin, conformational analysis, hydrogen bondsAbstract
We used classical molecular mechanics and dynamics simulations to sample the conformational space of maitotoxin, the largest and most lethal natural product. Among the set of minima obtained, the five conformers with the lowest energies show folded structures with an intramolecular hole. We found the folding mainly due to hydrogen bonds that fasten the mobile zones of the molecule. The hole on each MTX conformer is big enough to interact with ions, such as Ca2+ or Na+, which could be involved in its toxic effects observed on all cell types.
Downloads
Download data is not yet available.
References
1. Anderson, D.M. in Red Tides: Biology, Environmental Science and Toxicology; Okaichi, T., Anderson, D.M., Nemoto, T., Eds.; Elsevier: New York, 1994.
2. Murata, M.; Naoki, H.; Matsumaga, S.; Satake, M.; Yasumoto, T. J. Am. Chem. Soc. 1994, 116, 7098-7107.
3. Yasumoto, T.; Bagnis, R.; Vernoux, J.P. Bull. Jpn. Soc. Sci. Fish. 1976, 42, 359-365.
4. Zheng, W.; DeMaittei, J.A.; Wu, J.; Duan, J.W.; Cook, L.R.; Oinuma, H.; Kishi, Y. J. Am. Chem. Soc. 1996, 118, 7946-7968.
5. Kishi, Y. Pure and Appl. Chem. 1998, 70, 339-344.
6. Gallimore, A.R.; Spencer, J.B. Angew. Chem. Int. Ed. Engl. 2006, 45, 4406–4413.
7. Murata, M.; Yasumoto, T. Nat. Prod. Rep. 2000, 17, 293-314.
8. Yasumoto, T. Chem. Rec. 2001, 1, 228-242.
9. Nicolaou, K.C.; Frederick, M.O. Angew. Chem. Int. Ed. 2007, 46, 5278-5282.
10. Igarashi, T.; Aritake, S.; Yasumoto, T. Nat. Toxins 1999, 7, 71-79.
11. Gusovsky, F.; Daly, J.W. Biochem. Pharmacol. 1990, 39, 1633-1639.
12. Weber, W.M.; Popp, C.; Clauss, W.; Van Driessche, W. Eur. J. Physiol. 2000, 439, 363-369.
13. Diakov, A.; Koch, J.-P.; Ducoudret, O.; Müller-Berger, S.; Frönter, E. Eur. J. Physiol. 2001, 442, 700-708.
14. de la Rosa, L.A.; Alfonso, A.; Vilariño, N.; Vieytes, M.R.; Yasumoto, T.; Botana, L.M. Cell. Signalling 2001, 13, 711-716.
15. Martínez-François, J.R.; Morales-Tlalpan, V.; Vaca, L. J. Physiol. 2002, 538, 79-86.
16. Morales-Tlalpan, V.; Vaca, L. Toxicon 2002, 40, 493-500.
17. Treviño, C.L.; de la Vega-Beltrán, J.L.; Nishigaki, T.; Felix, R.; Darszon, A. J. Cell. Physiol. 2006, 206, 449-456.
18. Takahashi, M.; Ohizumi, Y.; Yasumoto, T. J. Biol. Chem. 1982, 257, 7287–7289.
19. Escobar, L.I.; Salvador, C.; Martínez, M.; Vaca, L. Neurobiology (Bp) 1998, 6, 59–74.
20. Yuhi, T., Wada, A.; Yamamoto, R.; Urabe, M.; Niina, H; Izumi, F.; Yanagita, T. Naunyn Schmiedebergs Arch. Pharmacol. 1994, 350, 209–212.
21. Baden, D.G. Faseb J. 1989, 3, 1807–1817.
22. Catterall, W.A.; Trainer, V.; Baden, D.G. Bull. Soc. Pathol. Exot. 1992, 85 (5 Pt 2), 481–485.
23. Scheiner-Bobis, G.; Heringdorf, D.M.Z.; Christ, M.; Habermann, E. Mol. Pharmacol. 1994, 45, 1132–1136.
24. Boyd, D.B.; Lipkowitz, K.B. J. Chem. Educ. 1982, 59, 269-274.
25. Rappé, A.K.; Casewit, C.J. Molecular Mechanics Across Chemistry, University Science Books, 1997.
26. Shi, S.; Yan, L.; Yang, Y.; Fisher-Shaulsky, J.; Thacher, T. J. Comp. Chem. 2003, 24, 1059-1076.
27. InsightII, Discover User Guide, Part 1, Molecular Simulations, San Diego, CA. 1996.
28. Kirkpatrick, S.; Gelatt, C.D.; Vecchi, M.P. Science 1983, 220, 671-680.
2. Murata, M.; Naoki, H.; Matsumaga, S.; Satake, M.; Yasumoto, T. J. Am. Chem. Soc. 1994, 116, 7098-7107.
3. Yasumoto, T.; Bagnis, R.; Vernoux, J.P. Bull. Jpn. Soc. Sci. Fish. 1976, 42, 359-365.
4. Zheng, W.; DeMaittei, J.A.; Wu, J.; Duan, J.W.; Cook, L.R.; Oinuma, H.; Kishi, Y. J. Am. Chem. Soc. 1996, 118, 7946-7968.
5. Kishi, Y. Pure and Appl. Chem. 1998, 70, 339-344.
6. Gallimore, A.R.; Spencer, J.B. Angew. Chem. Int. Ed. Engl. 2006, 45, 4406–4413.
7. Murata, M.; Yasumoto, T. Nat. Prod. Rep. 2000, 17, 293-314.
8. Yasumoto, T. Chem. Rec. 2001, 1, 228-242.
9. Nicolaou, K.C.; Frederick, M.O. Angew. Chem. Int. Ed. 2007, 46, 5278-5282.
10. Igarashi, T.; Aritake, S.; Yasumoto, T. Nat. Toxins 1999, 7, 71-79.
11. Gusovsky, F.; Daly, J.W. Biochem. Pharmacol. 1990, 39, 1633-1639.
12. Weber, W.M.; Popp, C.; Clauss, W.; Van Driessche, W. Eur. J. Physiol. 2000, 439, 363-369.
13. Diakov, A.; Koch, J.-P.; Ducoudret, O.; Müller-Berger, S.; Frönter, E. Eur. J. Physiol. 2001, 442, 700-708.
14. de la Rosa, L.A.; Alfonso, A.; Vilariño, N.; Vieytes, M.R.; Yasumoto, T.; Botana, L.M. Cell. Signalling 2001, 13, 711-716.
15. Martínez-François, J.R.; Morales-Tlalpan, V.; Vaca, L. J. Physiol. 2002, 538, 79-86.
16. Morales-Tlalpan, V.; Vaca, L. Toxicon 2002, 40, 493-500.
17. Treviño, C.L.; de la Vega-Beltrán, J.L.; Nishigaki, T.; Felix, R.; Darszon, A. J. Cell. Physiol. 2006, 206, 449-456.
18. Takahashi, M.; Ohizumi, Y.; Yasumoto, T. J. Biol. Chem. 1982, 257, 7287–7289.
19. Escobar, L.I.; Salvador, C.; Martínez, M.; Vaca, L. Neurobiology (Bp) 1998, 6, 59–74.
20. Yuhi, T., Wada, A.; Yamamoto, R.; Urabe, M.; Niina, H; Izumi, F.; Yanagita, T. Naunyn Schmiedebergs Arch. Pharmacol. 1994, 350, 209–212.
21. Baden, D.G. Faseb J. 1989, 3, 1807–1817.
22. Catterall, W.A.; Trainer, V.; Baden, D.G. Bull. Soc. Pathol. Exot. 1992, 85 (5 Pt 2), 481–485.
23. Scheiner-Bobis, G.; Heringdorf, D.M.Z.; Christ, M.; Habermann, E. Mol. Pharmacol. 1994, 45, 1132–1136.
24. Boyd, D.B.; Lipkowitz, K.B. J. Chem. Educ. 1982, 59, 269-274.
25. Rappé, A.K.; Casewit, C.J. Molecular Mechanics Across Chemistry, University Science Books, 1997.
26. Shi, S.; Yan, L.; Yang, Y.; Fisher-Shaulsky, J.; Thacher, T. J. Comp. Chem. 2003, 24, 1059-1076.
27. InsightII, Discover User Guide, Part 1, Molecular Simulations, San Diego, CA. 1996.
28. Kirkpatrick, S.; Gelatt, C.D.; Vecchi, M.P. Science 1983, 220, 671-680.
Downloads
Published
2019-07-29
Issue
Section
Regular Articles
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
