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Structural studies of shikimate dehydrogenase from Bacillus anthracis complexed with cofactor NADP

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Abstract

Bacillus anthracis has been employed as an agent of bioterrorism, with high mortality, despite anti-microbial treatment, which strongly indicates the need of new drugs to treat anthrax. Shikimate pathway is a seven step biosynthetic route which generates chorismic acid from phosphoenol pyruvate and erythrose-4-phosphate. Chorismic acid is the major branch point in the synthesis of aromatic amino acids, ubiquinone, and secondary metabolites. The shikimate pathway is essential for many pathological organisms, whereas it is absent in mammals. Therefore, these enzymes are potential targets for the development of nontoxic antimicrobial agents and herbicides and have been submitted to intensive structural studies. The forth enzyme of this pathway is responsible for the conversion of dehydroshikimate to shikimate in the presence of NADP. In order to pave the way for structural and functional efforts toward development of new antimicrobials we describe the molecular modeling of shikimate dehydrogenase from Bacillus anthracis complexed with the cofactor NADP. This study was able to identify the main residues of the NADP binding site responsible for ligand affinities. This structural study can be used in the design of more specific drugs against infectious diseases.

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References

  1. Casadevall A (2008) Front Biosci 13:4009

    Google Scholar 

  2. Oliveira JS, Sousa EHS, Basso LA, Palaci M, Dietze R, Santos DS et al (2004) Chem Commun (Camb) 7:312 doi:10.1039/b313592f

    Article  CAS  Google Scholar 

  3. Oliveira JS, Sousa EHS, Souza ON, Moreira IS, Santos DS, Basso LA (2006) Curr Pharm Des 12:2409 doi:10.2174/138161206777698927

    Article  CAS  Google Scholar 

  4. Oliveira JS, Vasconcelos IB, Moreira IS, Santos DS, Basso LA (2007) Curr Drug Targets 8:399 doi:10.2174/138945007780058942

    Article  CAS  Google Scholar 

  5. Dias MV, Vasconcelos IB, Prado AM, Fadel V, Basso LA, de Azevedo WF Jr et al (2007) Struct Biol 159:369 doi:10.1016/j.jsb.2007.04.009

    Article  CAS  Google Scholar 

  6. Vasconcelos IB, Meyer E, Sales FAM, Moreira IS, Basso LA, Santos DS (2008) Anti-infecive Agents in Medicinal Chemistry 7:50

    CAS  Google Scholar 

  7. Tipparaju SK, Jovasawal S, Forrester S, Mulhearn DC, Pegan S, Johnson ME et al (2008) Bioorg Med Chem Lett 18(12):3565 doi:10.1016/j.bmcl.2008.05.004

    Article  CAS  Google Scholar 

  8. Pereira JH, Vasconcelos JB, Oliveira JS, Caceres RA, de Azevedo WF Jr, Basso LA et al (2007) Curr Drug Targets 8:459 doi:10.2174/138945007780059013

    Article  CAS  Google Scholar 

  9. Dias MV, Faím LM, Vasconcelos IB, de Oliveira JS, Basso LA, Santos DS et al (2007) Acta Crystallogr Sect F Struct Biol Cryst Commun 63:1 doi:10.1107/S1744309106046823

    Article  CAS  Google Scholar 

  10. Silveira NJ, Uchoa HB, Pereira JH, Canduri F, Basso LA, Palma MS et al (2005) J Mol Model 11:160 doi:10.1007/s00894-005-0240-2

    Article  CAS  Google Scholar 

  11. Pereira JH, de Oliveira JS, Canduri F, Dias MV, Palma MS, Basso LA et al (2004) Acta Crystallogr D Biol Crystallogr 60:2310 doi:10.1107/S090744490402517X

    Article  CAS  Google Scholar 

  12. Segura-Cabrera A, Rodríguez-Pérez MA (2008) Bioorg Med Chem Lett 18(11):3152 doi:10.1016/j.bmcl.2008.05.003

    Article  CAS  Google Scholar 

  13. de Azevedo WF Jr (2007) Curr Drug Targets 8(3):387 doi:10.2174/138945007780058960

    Article  Google Scholar 

  14. Herrmann KM, Weaver LM (1999) Annu Rev Plant Physiol Plant Mol Biol 50:473–503 doi:10.1146/annurev.arplant.50.1.473

    Article  CAS  Google Scholar 

  15. Steinrucken HC, Amrhein N (1984) Eur J Biochem 14:351–357 doi:10.1111/j.1432-1033.1984.tb08379.x

    Article  Google Scholar 

  16. Schonbrunn E, Eschenburg S, Shuttleworth WA, Schloss JV, Amrhein N, Evans JN (2001) Proc Natl Acad Sci USA 98:1376–1380 doi:10.1073/pnas.98.4.1376

    Article  CAS  Google Scholar 

  17. Benach J, Lee I, Edstrom W, Kuzin AP, Chiang Y, Acton TB et al (2003) J Biol Chem 278:19176–19182 doi:10.1074/jbc.M301348200

    Article  CAS  Google Scholar 

  18. Shumilin I, Kretsinger R, Bauerle R (1999) Struct 7:865–875 doi:10.1016/S0969-2126(99)80109-9

    Article  CAS  Google Scholar 

  19. Carpenter EP, Hawkins AR, Frost JW, Brown KA (1998) Nature 394:299–302 doi:10.1038/28431

    Article  CAS  Google Scholar 

  20. Gourley DG, Shrive AK, Polikarpov I, Krell T, Coggins JR, Hawkins AR (1999) Nat Struct Biol 6:521–525 doi:10.1038/9287

    Article  CAS  Google Scholar 

  21. Michel G, Roszak AW, Sauve V, Maclean J, Matte A, Coggins JR (2003) J Biol Chem 278:19463–19472 doi:10.1074/jbc.M300794200

    Article  CAS  Google Scholar 

  22. Krell T, Coggins JR, Lapthorn AJ (1998) J Mol Biol 278:983–997 doi:10.1006/jmbi.1998.1755

    Article  CAS  Google Scholar 

  23. Stallings WC, Abdel-Maguid SS, Lim LW, Shie HS, Dayringer HE, Leimgruber NK (1991) Proc Natl Acad Sci USA 88:5046–5050 doi:10.1073/pnas.88.11.5046

    Article  CAS  Google Scholar 

  24. Maclean J, Ali S (2003) Structure 11:1499–1511 doi:10.1016/j.str.2003.11.005

    Article  CAS  Google Scholar 

  25. Bentley R (1990) Crit Rev Biochem Mol Biol 25(5):307–284 doi:10.3109/10409239009090615

    Article  CAS  Google Scholar 

  26. Roberts F, Roberts CW, Johnson JJ, Kyle DE, Krell T, Coggins C et al (1998) Nature 393:801–805 doi:10.1038/30718

    Article  CAS  Google Scholar 

  27. Roberts CW, Roberts F, Lyons RE, Kirisits MJ, Mui EJ, Finnerty J et al (2002) Infect Dis 185:25–36 doi:10.1086/338004

    Article  Google Scholar 

  28. Herrmann KM (1995) Plant Cell 7:907–919

    Article  CAS  Google Scholar 

  29. Murzin AG, Brenner SE, Hubbard T, Chothia C (1995) J Mol Biol 247:536–540

    CAS  Google Scholar 

  30. Baillie AC, Corbett JR, Dowsett JR, McCloskey P (1972) Biochem J 126:21

    Google Scholar 

  31. Deka RK, Anton IA, Dunbar B, Coggins JR (1994) FEBS Lett 349:397–402 doi:10.1016/0014-5793(94)00710-1

    Article  CAS  Google Scholar 

  32. Bagautdinov B, Kunishima N (2007) J Mol Biol 373:424–438 doi:10.1016/j.jmb.2007.08.017

    Article  CAS  Google Scholar 

  33. Kroemer RT, Doughty SW, Robinson AJ, Richards WG (1996) Protein Eng 9(6):493–498 doi:10.1093/protein/9.6.493

    Article  CAS  Google Scholar 

  34. Berman HM, Westbrook J, Feng Z, Gilliard G, Bhat TN, Weissig H et al (2000) Nucleic Acids Res 28:235–242 doi:10.1093/nar/28.1.235

    Article  CAS  Google Scholar 

  35. Fernandes CL, Breda A, Santos DS, Basso LA, Souza ON (2007) Comput Biol Med 37:149–158 doi:10.1016/j.compbiomed.2006.01.001

    Article  CAS  Google Scholar 

  36. Gasteiger E, Jung E, Bairoch A (2001) Curr Issues Mol Biol 3:47

    CAS  Google Scholar 

  37. Bairoch A, Apweiler R (2000) Nucleic Acids Res 28:45 doi:10.1093/nar/28.1.45

    Article  CAS  Google Scholar 

  38. Bairoch A, Apweiler RJ (1997) Mol Med 75:312

    CAS  Google Scholar 

  39. Uchoa HB, Jorge GE, da Silveira NJF, Camera JC Jr, Canduri A, de Azevedo WF (2004) Biochem Biophys Res Commun 325:1481–1486 doi:10.1016/j.bbrc.2004.10.192

    Article  CAS  Google Scholar 

  40. Sali A, Blundell TL (1993) J Mol Biol 234:779–815 doi:10.1006/jmbi.1993.1626

    Article  CAS  Google Scholar 

  41. Arcuri HA, Canduri F, Pereira JH, da Silveira NJF, Camara JC Jr, de Oliveira JS et al (1994) Biochem Biophys Res Commun 320:979–991 doi:10.1016/j.bbrc.2004.05.220

    Article  CAS  Google Scholar 

  42. Dias MVB, Ely F, Palma MS, De Azevedo WF Jr, Basso LA, Santos DS (2007) Curr Drug Targets 8:48–55 doi:10.2174/138945007780058924

    Google Scholar 

  43. Thompson JD, Higgins DG, Gibson TJ (1994) Nucleic Acids Res 22:4673–4680 doi:10.1093/nar/22.22.4673

    Article  CAS  Google Scholar 

  44. Marques MR, Pereira JH, Oliveira JS, Basso LA, Santos DS, De Azevedo WF Jr et al (2007) Curr Drug Targets 8:56–68 doi:10.2174/138945007780058951

    Google Scholar 

  45. Caceres RA, Timmers LFS, Dias R, Basso LA, Santos DS, de Azevedo WF (2008) Bioorg Med Chem 16(9):4984–4993 doi:10.1016/j.bmc.2008.03.044

    Article  CAS  Google Scholar 

  46. De Azevedo WF, Mueller-Dieckmann JH, Schulze-Gahmen U, Worland PJ, Sausville E, Kim SH (1996) Proc Natl Acad Sci USA 93:2735–2740 doi:10.1073/pnas.93.7.2735

    Article  Google Scholar 

  47. Wang R, Lai L, Wang S (2002) J Comput Aided J Mol Des 16:11 doi:10.1023/A:1016357811882

    Article  CAS  Google Scholar 

  48. Caceres RA, Macedo Timmers LF, Vivan AL, Schneider CZ, Basso LA, De Azevedo WF et al (2008) J Mol Model 14(5):427–434 doi:10.1007/s00894-008-0291-2

    Article  CAS  Google Scholar 

  49. Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) J Appl Cryst 26:283–291 doi:10.1107/S0021889892009944

    Article  CAS  Google Scholar 

  50. Wallace AC, Laskowski RA, Thornton JM (1995) Protein Eng 8:127–134 doi:10.1093/protein/8.2.127

    Article  CAS  Google Scholar 

  51. Gasteiger E, Gattiker A, Hoogland C, Ivany I, Appel RD, Bairoch A (2003) Nucleic Acids Res 31:3784–3788 doi:10.1093/nar/gkg563

    Article  CAS  Google Scholar 

  52. Humphrey W, Dalke A, Schulten K (1996) J Mol Graph 14:33–38 doi:10.1016/0263-7855(96)00018-5

    Article  CAS  Google Scholar 

  53. Delano WL, Lam JW (2005) Abstr Pap Am Chem Soc 230:1371–1372

    Google Scholar 

  54. Carugo O, Argos P (1997) Proteins 28:10–28 doi:10.1002/(SICI)1097-0134(199705)28:1<10::AID-PROT2>3.0.CO;2-N

    Article  CAS  Google Scholar 

  55. Vogan E (2003) Structure 11:902–903 doi:10.1016/S0969-2126(03)00165-5

    Article  CAS  Google Scholar 

  56. Arcuri HA, Borges JC, Fonseca IO, Pereira JH, Ruggiero-Neto J, Basso LA et al (2008) Proteins 72(2):720–730 doi:10.1002/prot.21953

    Article  CAS  Google Scholar 

  57. Gan J, Wu Y, Prabakaram P, Gu Y, Li Y, Andrykovich M et al (2007) Biochemistry 46:9513–9522 doi:10.1021/bi602601e

    Article  CAS  Google Scholar 

  58. Lim S, Schroder I, Monbouquette HG (2004) FEMS Microbiol Lett 238:101–106

    CAS  Google Scholar 

  59. Zhang X, Zhang S, Hao F, Lai X, Yu H, Huang Y et al (2005) Biochem Mol Biol 38:624–631

    Google Scholar 

  60. Han C, Wang L, Yu K, Chen L, Hu L, Chen K et al (2006) FEBS J 273:4682–4692 doi:10.1111/j.1742-4658.2006.05469.x

    Article  CAS  Google Scholar 

  61. Collaborative Computation Project, Number 4 (1994) Acta Crystallogr D Biol Crystallogr 50:760 doi:10.1107/S0907444994003112

    Google Scholar 

  62. Brändén CI (1980) Q Rev Biophys 13:317–338

    Article  Google Scholar 

  63. Lesk AM (1995) Curr Opin Struct Biol 5:775–783 doi:10.1016/0959-440X(95)80010-7

    Article  CAS  Google Scholar 

  64. Canduri F, Teodoro LGVL, Lorenzi CCB, Hial V, Gomes RAS, Ruggiero Neto J et al (2001) Acta Crystallogr 57:1560–1570

    CAS  Google Scholar 

  65. De Azevedo WF Jr, Mueller-Dieckmann HJ, Schulze-Gahmen U, Worland PJ, Sausville E, Kim SH (1996) Proc Natl Acad Sci USA 93(7):2735–2740 doi:10.1073/pnas.93.7.2735

    Article  Google Scholar 

  66. De Azevedo WF Jr, Leclerc S, Meijer L, Havlicek L, Strnad M, Kim SH (1997) Eur J Biochem 243:518–526 doi:10.1111/j.1432-1033.1997.0518a.x

    Article  Google Scholar 

  67. De Azevedo WF Jr, Canduri F, Fadel V, Teodoro LGVL, Hial V, Gomes RAS (2001) Biochem Biophys Res Commun 287(1):277–281

    Article  CAS  Google Scholar 

  68. De Azevedo WF Jr, Canduri F, da Silveira NJF (2002) Biochem Biophys Res Commun 293(1):566–571 doi:10.1016/S0006-291X(02)00266-8

    Article  Google Scholar 

  69. Kim SH, Schulze-Gahmen U, Brandsen J, de Azevedo WF Jr (1996) Prog Cell Cycle Res 2:137–145

    CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from CNPq, CAPES and Instituto do Milênio (CNPq-MCT). WFA is senior researcher of CNPq (Conselho Nacional de Pesquisas, Brazil).

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Authors and Affiliations

  1. Faculdade de Biociências, Laboratório de Bioquímica Estrutural, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Guy Barros Barcellos, Rafael Andrade Caceres & Walter Filgueira de Azevedo Jr.

  2. Programa de Pós Graduação em Medicina e Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Rafael Andrade Caceres

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  1. Guy Barros Barcellos
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  2. Rafael Andrade Caceres
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  3. Walter Filgueira de Azevedo Jr.
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Correspondence to Walter Filgueira de Azevedo Jr..

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Barcellos, G.B., Caceres, R.A. & de Azevedo, W.F. Structural studies of shikimate dehydrogenase from Bacillus anthracis complexed with cofactor NADP. J Mol Model 15, 147–155 (2009). https://doi.org/10.1007/s00894-008-0403-z

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