Journal of Integrative Natural Science (통합자연과학논문집)

The Basic Science Institute Chosun University (조선대학교 기초과학연구원)
권호 표지
DOI QR코드

DOI QR Code

Comparative Modeling Studies of 1-deoxy-D-xylulose 5-phosphate Synthase (MEP pathway) from Mycobacterium Tuberculosis

  • Kothandan, Gugan (Department of Biohemistry, Centre for Bioinformatics, University of Madras, Guindy campus)
  • Received : 2011.07.12
  • Accepted : 2011.08.31
  • Published : 2011.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Tuberculosis is a major health problem in humans because of its multidrug resistance and discovering new treatments for this disease is urgently required. The synthesis of isoprenoids in Mycobacterium tuberculosis has been reported as an interesting pathway to target. In this context, 2C-methyl-D-erythritol 4-phosphate (MEP) pathway of M. tuberculosis has drawn attention. The MEP pathway begins with the condensation of glyceraldehyde 3-phosphate and pyruvate forming 1-deoxy-D-xylulose 5-phosphate (DXP) which is catalyzed by 1-deoxy-D-xylulose 5-phosphate synthase (DXS). As there is no X-ray structure was reported for this target, comparative modeling was used to generate the three dimensional structure. The structure was further validated by PROCHECK, VERIFY-3D, PROSA, ERRAT and WHATIF. Molecular docking studies was performed with the substrate (Thiamine pyrophosphate) and the reported inhibitor 2-methyl-3-(4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolol[1,5-a]pyrimidin-7-one) against the developed model to identify the crucial residues in the active site. This study may further be useful to provide structure based drug design.

Keywords

References

  1. www.tballiance.org
  2. I. Smith, "Mycobacterium tuberculosis pathogenesis and molecular determinants of virulence", Clin Microbiol Rev, Vol. 16, pp. 463-496, 2003. https://doi.org/10.1128/CMR.16.3.463-496.2003
  3. C. J. Murray and J. A. Salomon, "Modeling the impact of global tuberculosis control strategies", Proc Natl Acad Sci, Vol. 95, pp. 13881-13386, 1998. https://doi.org/10.1073/pnas.95.23.13881
  4. C. J. Murray, E. Dejonghe, H. J. Chum, D. S. Nyangulu, A. Salomao and K. Styblo, "Cost effectiveness of chemotherapy for pulmonary tuberculosis in three sub saharan african countries", Lancet, Vol. 338, pp. 1305-1308, 1991. https://doi.org/10.1016/0140-6736(91)92600-7
  5. A. Jindani, A. J. Nunn and D.A. Enarson, "Two 8- month regimens of chemotherapy for treatment of newly diagnosed pulmonary tuberculosis: international multicentre randomized trial", Lancet Vol. 364, pp. 1244-1251, 2004. https://doi.org/10.1016/S0140-6736(04)17141-9
  6. R. J. O'Brien and P. P. Nunn, "The need for new drugs against tuberculosis. Obstacles, opp.ortunities and next steps", Am J Respir Crit Care Med, Vol. 162, pp. 1055-1058, 2001.
  7. J. S. Mukherjee, M. L. Rich, A. R. Socci, J. K. Joseph, F. A. Viru, S. S. Shin, J. J. Furin, M. C. Becerra, D. J. Barry, J. Y. Kim, J. Bayona, P. Farmer, M. C. S. Fawzi and Seung KJ "Programs and principles in treatment of multidrug-resistant tuberculosis", Lancet, Vol. 363, pp. 474-481, 2004. https://doi.org/10.1016/S0140-6736(04)15496-2
  8. B. A. Wolucka, M. R. McNeil, E. Hoffmann, T. Chojnacki and P. J. Brennan "Recognition of the lipid intermediate for arabinogalactan/arabinomannan biosynthesis and its relation to the mode of action of ethambutol on mycobacteria", J Biol Chem, Vol. 269, pp. 23328-23335, 1994.
  9. K. Mikusova, M. Mikus, G. S. Besra, I. Hancock and P. J. Brennan, "Biosynthesis of the linkage region of the mycobacteria cell wall region", J Biol Chem, Vol. 271, pp. 7820-7828, 1996. https://doi.org/10.1074/jbc.271.13.7820
  10. S. Mahapatra, T. Yagi, J. T. Belisle, B. J. Espinosa, P. J. Hill, M. R. McNeil, P. J. Brennan and D. C. Crick, "Mycobacterial lipid II is composed of a complex mixture of modified muramyl and peptide moieties linked to decaprenyl phosphate", J Bacteriol, Vol. 187, pp. 2747-2757, 2005. https://doi.org/10.1128/JB.187.8.2747-2757.2005
  11. M. D. Collins, T. Pirouz, M. Goodfellow and D. E. Minnikin, "Distribution of menaquinones in actinomycetes and corynebacteria", J Gen Microbiol, Vol. 100 pp. 221-230, 1977. https://doi.org/10.1099/00221287-100-2-221
  12. J. C. Sacchettini, C. D. Poulter, "Creating isoprenoid diversity", Science, Vol. 277, pp. 1788-1789, 1997. https://doi.org/10.1126/science.277.5333.1788
  13. D. A. Bochar, J.A. Freisen, C. V. Stauffacher and V. W. Rodwell, "In: comprehensive natural products chemistry", Pergamon, Oxford, 1999.
  14. C. A. Testa and M. J. Brown "The methylerythritol phosphate pathway and its significance as a novel drug target", Curr Pharm Biotechnol, Vol. 4, pp. 248-259, 2003. https://doi.org/10.2174/1389201033489784
  15. M. Rodriguez-Concepcion, "The MEP pathway: a new target for the development of herbicides, antibiotics and antimalarial drugs", Curr Pharm Des, Vol. 10, pp. 2391-2400, 2004. https://doi.org/10.2174/1381612043384006
  16. H. Eoh, P. J. Brennan and D. C. Crick "The Mycobacterium tuberculosis MEP (2C-methyl-D-erythritol 4-phosphate) pathway as a new drug target", Tuberculosis, Vol. 89, pp. 1-11, 2008.
  17. G. A. Sprenger, U. Schörken, T. Wiegert, S. Grolle, A. A. De Graaf, S. V. Taylor, T. P. Begley, S. Bringer-Meyer and H. Sahm "Identification of a thiamin- dependent synthase Escherichia coli required for the formation of 1-deoxy-D-xylulose 5-phosphate precursor to isoprenoids, thiamin and piridoxol", Proc Natl Acad Sci USA, Vol. 94, pp. 12857-12862, 1997. https://doi.org/10.1073/pnas.94.24.12857
  18. L. M. Lois, N. Campos, S. R. Putra, K. Danielsen, M. Rohmer and A. Boronat, "Cloning and characterization of a gene from Escherichia coli encoding a transketolase-like enzyme that catalyzes the synthesis of D-1-deoxyxylulose 5-phosphate, a common precursor for isoprenoid, thiamin, and pyridoxol biosynthesis", Proc Natl Acad Sci USA, Vol. 95, pp. 2105-2110, 1998. https://doi.org/10.1073/pnas.95.5.2105
  19. B. M. Lange, M. R. Wildung, D. McCaskill and R. Croteau, "A family of transketolases that directs isoprenoid biosynthesis via a mevalonate-independent pathway", Proc Natl Acad Sci USA, Vol. 95 pp. 2100-2104, 1998. https://doi.org/10.1073/pnas.95.5.2100
  20. S. Nidhi, A. A. Mitchell, R. M. Christopher, "Towards Mycobacterium tuberculosis inhibitor design: homology modeling and molecular dynamics simulation", J Comput Aided Mol Des, Vol. 21 pp. 511- 522, 2007. https://doi.org/10.1007/s10822-007-9132-0
  21. O. Cristian, C. Alex, R. Jamie and I. Santiago, "Homology modeling of Mycobacreium tuberculosis 2C-methyl-D-erythiritol-4-phosphate cytidyltransferase", J Mol Model, Vol. 16, pp. 1061-1073, 2010. https://doi.org/10.1007/s00894-009-0615-x
  22. R. E. Hill, K. Himmeldirk, I. A. Kennedy, R. M. Pauloski, B. G. Sayer, E. Wolf and I. D. Spenser, The Biogenetic Anatomy of Vitamin B6 A 13C NMR investigation of biosynthesis of pyridoxil in Escherichia coli, J Biol Chem, Vol. 271, pp. 30426-30435, 1996. https://doi.org/10.1074/jbc.271.48.30426
  23. M. Therisod, J. C. Fischer and B. Estramareix, The origin of the carbon chain in the thiazole moiety of thiamine in Escherichia coli: incorporation of deuterated 1-deoxy-D-threo-2-pentulose, Biochem Biophys Res Commun, Vol. 98, pp. 374-379, 1991.
  24. R. H. White, "The biosynthetic origin of the carbon and hydrogen atoms in the thiazole moiety of thiamin in Escherichia coli", Biochemistry, Vol. 17, pp. 3833-3840, 1978. https://doi.org/10.1021/bi00611a024
  25. J. Mao, H. Eoh, R. He, Y. Wang, B. Wan, S. G. Franzblau, C. D. Crick and A. P. Kozilkowski, "Structure activity relationships of compounds targeting Mycobacterium tuberculosis 1-deoxy-Dxylulose 5- phosphate synthase", Bioorganic and Medicinal Chemistry Letters, Vol. 18, pp. 5320-5323, 2008. https://doi.org/10.1016/j.bmcl.2008.08.034
  26. C. M. Sassetti, D. H. Boyd and E. Rubin, "Genes required for mycobacterial growth defined by high density mutagenesis", J Mol Microbiol, Vol. 48, pp. 77-84, 2003. https://doi.org/10.1046/j.1365-2958.2003.03425.x
  27. S. Xiang, G. Usunow, G. Lange, M. Busch and L. Tong, "Crystal structure of 1-deoxy-D-xylulose 5- phosphate synthase, a crucial enzyme for isoprenoids biosynthesis", J Biol Chem, Vol. 282, pp. 2676-2682, 2007. https://doi.org/10.1074/jbc.M610235200
  28. A. Sali and T. L. Blundell, "Comparative protein modelling by satisfaction of spatial restraints", J Mol Biol, Vol. 234, pp. 779-815, 1993. https://doi.org/10.1006/jmbi.1993.1626
  29. A. Sali and J. P. Overington, "Derivation of rules for comparative protein modeling from a database of protein structure alignments", Protein Sci, Vol. 3, pp. 1582-1596, 1994. https://doi.org/10.1002/pro.5560030923
  30. A. Sali, "Modeling mutations and homologous proteins", Curr Opin Biotechnol, Vol. 6, pp. 437-451, 1995. https://doi.org/10.1016/0958-1669(95)80074-3
  31. A. Sali, L. Potterton, F. Yuan, H. van Vlijmen, and M. Karplus, "Evaluation of comparative protein modeling by MODELLER", Proteins, Vol. 23, pp. 318-326, 1995. https://doi.org/10.1002/prot.340230306
  32. R. A. Laskowski, M. W. MacArthur, D. S. Moss, and J. M. Thornton, "PROCHECK: a program to check the stereochemical quality of protein structures", J. Appl. Cryst., Vol. 26, pp. 283-291, 1993. https://doi.org/10.1107/S0021889892009944
  33. C. Colovos and T. O. Yeates, "Verification of protein structures: patterns of non-bonded atomic interactions", Protein Sci, Vol. 2, pp. 1511-1519, 1993. https://doi.org/10.1002/pro.5560020916
  34. G. Vriend and C. Sander, "Quality-control of protein modelsdirectional atomic contact analysis", J App.l Cryst, Vol. 26, pp. 47-60, 1993. https://doi.org/10.1107/S0021889892008240
  35. K. Tomii, T. Hirokawa and C. Motono, "Protein structure prediction using a variety of profile libraries and 3D verification", Proteins, Vol. 61, pp. 114- 121, 2005. https://doi.org/10.1002/prot.20727
  36. J. U. Bowie, R. Luthy and D. Eisenberg, "A method to identify protein sequences that fold into a known three-dimensional structure", Science, Vol. 253, pp. 164-170, 1991. https://doi.org/10.1126/science.1853201
  37. R. Luthy, J. U. Bowie and D. Eisenberg, "Assessment of protein models with three-dimensional profiles", Nature, Vol. 356, pp. 83-85, 1992. https://doi.org/10.1038/356083a0
  38. G. M. Morris, D. S. Goodsell, R. S. Halliday, R. Huey, W. E. Hart, R. K. Belew and A. J. Olson, "Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function", J Comput Chem, Vol. 19, pp. 1639-1662, 1992.
  39. W. L. Delano, "The PYMOL molecular graphics system", Palo Alto CA, 2002.