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Probing the Binding of Syzygium-Derived α-Glucosidase Inhibitors with N- and C-Terminal Human Maltase Glucoamylase by Docking and Molecular Dynamics Simulation

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Abstract

Human maltase glucoamylase (MGAM) is a potent molecular target for controlling post prandial glucose surplus in type 2 diabetes. Binding of small molecules from Syzygium sp. with α-glucosidase inhibitory potential in MGAM has been investigated in silico. Our results suggest that myricetin was the most potent inhibitor with high binding affinity for both N- and C-terminals of MGAM. Molecular dynamics revealed that myricetin interacts in its stretched conformation through water-mediated interactions with C-terminal of MGAM and by normal hydrogen bonding with the N-terminal. W1369 of the extended 21 amino acid residue helical loop of C-terminal plays a major role in myricetin binding. Owing to its additional sugar sites, overall binding of small molecules favours C-terminal MGAM.

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References

  1. Åqvist, J., & Hansson, T. (1996). The Journal of Physical Chemistry, 100, 9512–9521.

    Article  Google Scholar 

  2. Asano, N. (2003). Glycobiology, 13, 93R–104R.

    Article  CAS  Google Scholar 

  3. Beecher, G. R. (2003). Journal of Nutrition, 133, 3248S–3254S.

    CAS  Google Scholar 

  4. Benalla, W., Bellahcen, S., & Bnouham, M. (2010). Current Diabetes Review, 6, 247–254.

    Article  CAS  Google Scholar 

  5. Ceriello, A. (2005). Diabetes, 54, 1–7.

    Article  CAS  Google Scholar 

  6. Cortés Cabrera, A., & Rueda Pérez, C. (2010) Anales de la Real Academia Nacional de Farmacia, pp. 3.

  7. Goodsell, D. S., Morris, G. M., & Olson, A. J. (1996). Journal of Molecular Recognition, 9, 1–5.

    Article  CAS  Google Scholar 

  8. Grover, J. K., Yadav, S., & Vats, V. (2002). Journal of Ethnopharmacology, 81, 81–100.

    Article  CAS  Google Scholar 

  9. Gunther, S., Wehrspaun, A., & Heymann, H. (1996). Archives of Biochemistry & Biophysics, 327, 295–302.

    Article  CAS  Google Scholar 

  10. Helmstadter, A. (2008). Die Pharmazie-An International Journal of Pharmaceutical Sciences, 63, 91–101.

    CAS  Google Scholar 

  11. Hornak, V., Abel, R., Okur, A., Strockbine, B., Roitberg, A., & Simmerling, C. (2006). Proteins, 65, 712–725.

    Article  CAS  Google Scholar 

  12. Lattig, J., Bohl, M., Fischer, P., Tischer, S., Tietbohl, C., Menschikowski, M., et al. (2007). Journal of Computer Aided Molecular Design, 21, 473–483.

    Article  Google Scholar 

  13. Manaharan, T., Appleton, D., Cheng, H. M., & Palanisamy, U. D. (2012). Food Chemistry, 132, 1802–1807.

    Article  CAS  Google Scholar 

  14. Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., et al. (2009). Journal of Computational Chemistry, 30, 2785–2791.

    Article  CAS  Google Scholar 

  15. Nichols, B. L., Avery, S., Sen, P., Swallow, D. M., Hahn, D., & Sterchi, E. (2003). Proceedings of the National Academy of Sciences of the United States of America, 100, 1432–1437.

    Article  CAS  Google Scholar 

  16. Nichols, B. L., Eldering, J., Avery, S., Hahn, D., Quaroni, A., & Sterchi, E. (1998). Journal of Biological Chemistry, 273, 3076–3081.

    Article  CAS  Google Scholar 

  17. Nichols, B. L., Quezada-Calvillo, R., Robayo-Torres, C. C., Ao, Z., Hamaker, B. R., Butte, N. F., et al. (2009). Journal of Nutrition, 139, 684–690.

    Article  CAS  Google Scholar 

  18. Oliveira, A. C., Endringer, D. C., Amorim, L. A., das Gracas, L. B. M., & Coelho, M. M. (2005). Journal of Ethnopharmacology, 102, 465–469.

    Article  Google Scholar 

  19. Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., et al. (2004). Journal of Computational Chemistry, 25, 1605–1612.

    Article  CAS  Google Scholar 

  20. Quezada-Calvillo, R., Sim, L., Ao, Z., Hamaker, B. R., Quaroni, A., Brayer, G. D., et al. (2008). Journal of Nutrition, 138, 685–692.

    CAS  Google Scholar 

  21. Ren, L., Cao, X., Geng, P., Bai, F., & Bai, G. (2011). Carbohydrate Research, 346, 2688–2692.

    Article  CAS  Google Scholar 

  22. Ren, L., Qin, X., Cao, X., Wang, L., Bai, F., Bai, G., et al. (2011). Protein & Cell, 2, 827–836.

    Article  CAS  Google Scholar 

  23. Samadder, A., Chakraborty, D., De, A., Bhattacharyya, S. S., Bhadra, K., & Khuda-Bukhsh, A. R. (2011). European Journal of Pharmaceutical Sciences, 44, 207–217.

    Article  CAS  Google Scholar 

  24. Sharma, S. B., Nasir, A., Prabhu, K. M., & Murthy, P. S. (2006). Journal of Ethnopharmacology, 104, 367–373.

    Article  Google Scholar 

  25. Sharma, S. B., Nasir, A., Prabhu, K. M., Murthy, P. S., & Dev, G. (2003). Journal of Ethnopharmacology, 85, 201–206.

    Article  CAS  Google Scholar 

  26. Shinde, J., Taldone, T., Barletta, M., Kunaparaju, N., Hu, B., Kumar, S., et al. (2008). Carbohydrate Research, 343, 1278–1281.

    Article  CAS  Google Scholar 

  27. Sim, L., Quezada-Calvillo, R., Sterchi, E. E., Nichols, B. L., & Rose, D. R. (2008). Journal of Molecular Biology, 375, 782–792.

    Article  CAS  Google Scholar 

  28. Sousa da Silva, A. W., & Vranken, W. F. (2012). BMC Research Notes, 5, 367.

    Article  Google Scholar 

  29. Srivastava, S., & Chandra, D. (2013). Journal of the Science of Food and Agriculture, 93(9), 2084–2093.

    Article  CAS  Google Scholar 

  30. Teixeira, C. C., Pinto, L. P., Kessler, F. H., Knijnik, L., Pinto, C. P., Gastaldo, G. J., et al. (1997). Journal of Ethnopharmacology, 56, 209–213.

    Article  CAS  Google Scholar 

  31. Teixeira, C. C., Weinert, L. S., Barbosa, D. C., Ricken, C., Esteves, J. F., & Fuchs, F. D. (2004). Diabetes Care, 27, 3019–3020.

    Article  Google Scholar 

  32. Van de Laar, F.A., Lucassen, P.L., Akkermans, R.P., Van de Lisdonk, E.H., Rutten, G.E., & Van Weel, C. (2005). Cochrane Database of Systematic Reviews, CD003639.

  33. Wang, J., Wang, W., Kollman, P. A., & Case, D. A. (2006). Journal of Molecular Graphics and Modelling, 25, 247–260.

    Article  Google Scholar 

  34. Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A., & Case, D. A. (2004). Journal of Computational Chemistry, 25, 1157–1174.

    Article  CAS  Google Scholar 

  35. Yoshikawa, M., Morikawa, T., Matsuda, H., Tanabe, G., & Muraoka, O. (2002). Bioorganic & Medicinal Chemistry, 10, 1547–1554.

    Article  CAS  Google Scholar 

  36. Yoshikawa, M., Murakami, T., Yashiro, K., & Matsuda, H. (1998). Chemical & pharmaceutical bulletin, 46, 1339.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank the School of Biosciences and Technology, VIT University for providing funds and infrastructure for this work. We gratefully acknowledge the CDAC supercomputing grid facility, BRAF for providing cluster computer network for running the simulations.

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Authors and Affiliations

  1. 206, Structural Biology Lab, Centre for Biomedical Research, School of Bio Sciences & Technology, VIT University, Vellore, 632014, Tamil Nadu, India

    Debasish Roy, Vinod Kumar & Kavitha Thirumurugan

  2. Shodhaka Life Sciences Pvt. Ltd, IBAB Biotech Park, Electronic City, Phase 1, Bengaluru (Bangalore), 560100, Karnataka, India

    Vinod Kumar & Kshitish K. Acharya

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  1. Debasish Roy
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  2. Vinod Kumar
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  3. Kshitish K. Acharya
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Correspondence to Kavitha Thirumurugan.

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Roy, D., Kumar, V., Acharya, K.K. et al. Probing the Binding of Syzygium-Derived α-Glucosidase Inhibitors with N- and C-Terminal Human Maltase Glucoamylase by Docking and Molecular Dynamics Simulation. Appl Biochem Biotechnol 172, 102–114 (2014). https://doi.org/10.1007/s12010-013-0497-3

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