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Structural Insights on Mycobacterium tuberculosis Thiazole Synthase—A Molecular Dynamics/Docking Approach

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Abstract

Tuberculosis (TB), an epidemic disease, affects the world with death rate of two million people every year. The bacterium Mycobacterium tuberculosis was found to be a more potent and disease-prolonged bacterium among the world due to multi-drug resistance. Emergence of new drug targets is needed to overcome the bacterial resistance that leads to control epidemic tuberculosis. The pathway thiamine biosynthesis was targeting M. tuberculosis due to its role in intracellular growth of the bacterium. The screening of enzymes involved in thiamin biosynthesis showed novel target thiazole synthase (ThiG) involved in catalysis of rearrangement of 1-deoxy-d-xylulose 5-phosphate (DXP) to produce the thiazole phosphate moiety of thiamine. We carried out homology modeling for ThiG to understand the structure–function relationship, and the model was refined with MD simulations. The results showed that the model predicted with (α + β)8-fold of synthase family proteins. Molecular docking of ThiG model with substrate DXP showed binding mode and key residues ARG46, ASN69, THR41, and LYS96 involved in the catalysis. First-line anti-tuberculosis drugs were docked with ThiG to identify the inhibition. The report showed the anti-tuberculosis drugs interact well with ThiG which may lead to block thiamin biosynthesis pathway.

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References

  1. Kaufmann, S. H. (2006). Nature Reviews Immunology, 6(9), 699–704.

    Article  CAS  Google Scholar 

  2. Suheir, E., Abedelmajeed, N., Kifaya, A., Ziad, A., Greenblatt, C. L., Spigelman, M., et al. (2012). BMC Research Notes, 5, 270–278.

    Article  Google Scholar 

  3. Pai, M., & O’Brien, R. (2006). Expert Review of Molecular Diagnostics, 6, 509–514.

    Article  Google Scholar 

  4. Sharma, S. K., & Mohan, A. (2004). Indian Journal of Medical Research, 120, 354–376.

    CAS  Google Scholar 

  5. Freire, M. C. (2006). World Hospitals and Health Services, 42(1), 34–7.

    Google Scholar 

  6. Raviglione, M. C., & O’Brien, R. J. (2005). Harrison’s principles of internal medicine., 16, 953–66.

    Google Scholar 

  7. Iyawoo, K. (2004). Tuberculosis (Edinburgh, Scotland), 84(1–2), 4–7.

    Article  Google Scholar 

  8. Dony, J. F., Jamaliah, A., & Yap, K. T. (2004). Tuberculosis, 84, 8–18.

    Article  Google Scholar 

  9. Cole, S. T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., et al. (1998). Nature, 393(6685), 537–544.

    Article  CAS  Google Scholar 

  10. Puneet Chopra, L. S., Madhur, M. S., & Singh, Y. (2003). Indian Journal of Medical Research, 117, 1–9.

    Google Scholar 

  11. Dugas, H. (1996). Bioorganic chemistry. In C. R. Cantor (Ed.), A chemical approach to enzyme action (third edition) (pp. 560–573). New York: Springer-Verlag.

  12. Singleton, C. K., & Martin, P. R. (2001). Current Molecular Medicine, 1, 197–207.

    Article  CAS  Google Scholar 

  13. Park, J. H., Dorrestein, P. C., Zhai, H., Kinsland, C., McLafferty, F. W., & Begley, T. P. (2003). Biochemistry, 42, 12430–12438.

    Article  CAS  Google Scholar 

  14. Xi, J., Ge, Y., Kinsland, C., McLafferty, F. W., & Begley, T. P. (2001). Proceedings of the National Academy of Sciences, 8, 8513–8518.

    Article  Google Scholar 

  15. Settembre, E. C., Dorrestein, P. C., Chatterjee, A., McLafferty, F. W., Begley, T. P., & Ealick, S. E. (2004). Biochemistry, 43, 11647–11657.

    Article  CAS  Google Scholar 

  16. Sali, A., & Blundell, T. L. (1993). Journal of Molecular Biology, 234, 779–815.

    Article  CAS  Google Scholar 

  17. Delano, WL, (2002). http://www.pymol.org.

  18. Laskowski, R. A., MacArthur, M. W., Moss, D. S., & Thornton, J. M. (1993). Journal of Applied Crystal., 26, 283–291.

    Article  CAS  Google Scholar 

  19. Luthy, R., Bowie, J. U., & Eisenberg, D. (1992). Nature, 356, 83–85.

    Article  CAS  Google Scholar 

  20. Wiederstein, M., & Sippl, M. J. (2007). Nucleic Acids Research, 35, 407–410.

    Article  Google Scholar 

  21. Ramachandran, G. N., Ramakrishnan, C., & Sasisekharan, V. (1963). Journal of Molecular Biology, 7, 95–9.

    Article  CAS  Google Scholar 

  22. Berendsen, H. J. C., van der Spoel, D., & van Drunen, R. (1995). Computed Physics Communication, 91, 43–56.

    Article  CAS  Google Scholar 

  23. Trott, O., & Olson, A. J. (2010). Journal of Computational Chemistry, 31, 455–461.

    CAS  Google Scholar 

  24. Alasdair, T., Laurie, R., & Jackson, R. M. (2005). Bioinformatics, 21(9), 1908–1916.

    Article  Google Scholar 

  25. Assam-Assam, J. P., Penlap, V. B., Cho-Ngwa, F., Tedom, J. C., Ane-Anyangwe, I., & Titanji, V. P. (2011). BMC Infectious Diseases, 11, 94–100.

    Article  CAS  Google Scholar 

  26. ACD/ChemSketch 10.0, (2006). Advanced Chemistry Development, Inc., Toronto, ON, Canada, http://www.acdlabs.com.

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Authors and Affiliations

  1. Unit of Biochemistry, Faculty of Medicine, AIMST University, Bedong, 08100, Kedah, Malaysia

    K. Rohini

  2. Unit of Psychiatry, Faculty of Medicine, AIMST University, Bedong, Kedah, Malaysia

    P. S. Srikumar

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  1. K. Rohini
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  2. P. S. Srikumar
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Correspondence to K. Rohini.

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Rohini, K., Srikumar, P.S. Structural Insights on Mycobacterium tuberculosis Thiazole Synthase—A Molecular Dynamics/Docking Approach. Appl Biochem Biotechnol 169, 1790–1798 (2013). https://doi.org/10.1007/s12010-013-0110-9

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  • DOI: https://doi.org/10.1007/s12010-013-0110-9

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