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Dbmodeling

A database applied to the study of protein targets from genome projects

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Abstract

Genome sequencing efforts are providing us with complete genetic blueprints for hundreds of organisms. We are now faced with assigning, understanding, and modifying the functions of proteins encoded by these genomes. DBMODELING is a relational database of annotated comparative protein structure models and their metabolic pathway characterization, when identified. This procedure was applied to complete genomes such as Mycobacterium tuberculosis and Xylella fastidiosa. The main interest in the study of metabolic pathways is that some of these pathways are not present in humans, which makes them selective targets for drug design, decreasing the impact of drugs in humans. In the database, there are currently 1116 proteins from two genomes. It can be accessed by any researcher at http://www. biocristalografia.df.ibilce. unesp.br/tools/. This project confirms that homology modeling is a useful tool in structural bioinformatics and that it can be very valuable in annotating genome sequence information, contributing to structural and functional genomics, and analyzing protein-ligand docking.

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References

  1. da Silveira, N. J. F., Uchôa, H. B., Pereira, J. H., et al. (2005) Molecular models of protein targets from Mycobacterium tuberculosis. J. Mol. Model 11, 160–166.

    Article  PubMed  Google Scholar 

  2. Word Health Organization (2001) Global tuberculosis control. WHO Report 2001, Geneva, Switzerland, WHO/ CDS/TB/2001, 287.

  3. Simpson, A. J., Reinach, F. C., Arruda, P., et al. (2002) The genome sequence of the plant pathogen Xylella fastidiosa. Nature 406, 151–157.

    Google Scholar 

  4. Bevan, M. (2002) The bugs from Brazil. Nature 406, 140–141.

    Article  Google Scholar 

  5. Ealick, S. E., Babu, Y. S., Bugg, C. E., et al., (1991) Application of crystllographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors. Proc. Natl. Acad. Sci. U.S.A. 88, 11,540–11,544.

    Article  CAS  Google Scholar 

  6. Veerapandian, P. (1997) Structure-Based Drug Design (Veerapandian, P., ed.), Marcel Dekker, New York.

    Google Scholar 

  7. de Azevedo, W. F., Jr., Mueller-Dieckmann, H. J., Schulze-Gahmen, U., Worland, P. J., Sausville, E., and Kim, S. H. (1996) Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Proc. Natl. Acad. Sci. U.S.A. 93, 2735–2740.

    Article  PubMed  Google Scholar 

  8. de Azevedo, W. F., Jr., Leclerc, S., Meijer, L., Havlicek, L., Strnad, M., and Kim, S. H. (1997) Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine. Eur. J. Biochem. 243, 518–526.

    Article  PubMed  Google Scholar 

  9. Foster, M. J. (2002) Molecular modeling in structural biology. Micron 33, 365–384.

    Article  Google Scholar 

  10. Ring, C. S., Sun, E., McKerrow, J. G., Lee, G. K., Rosenthal, P. J., Kuntz, I. D., and Cohen, F. E. (1993) Structure-based inhibitor design by using protein models for the development of antiparasitic agents. Proc. Natl. Acad. Sci. U.S.A. 90, 3583–3587.

    Article  PubMed  CAS  Google Scholar 

  11. Selzer, P. M., Chen, X., Chan, V. J., et al. (1997) Leishmania major: molecular modeling of cysteine proteases and prediction of new nonpeptide inhibitors. Exp. Parasitol. 87, 212–221.

    Article  PubMed  CAS  Google Scholar 

  12. Que, X., Brinen, L. S., Perkins, P., et al. (2002) Cysteine proteinases from distinct cellular compartments are recruited to phagocytic vesicles by Entamoeba histolytica. Mol. Biochem. Parasitol. 119, 23–32.

    Article  PubMed  CAS  Google Scholar 

  13. Sali, A. and Blundell, T. L. (1993) Comparative protein modelling by satisfaction of spatial restriants. J. Mol. Biol. 234, 779–815.

    Article  PubMed  CAS  Google Scholar 

  14. Blundell, T. L., Jhoti, H., and Abell, C. (2002) High-throughput crystallography for lead discovery in drug design. Nat. Rev. 1, 45–54.

    CAS  Google Scholar 

  15. Jacobson, M. and Sali, A. (2004) Comparative protein structure modeling and its applications to drug discovery. Annu. Rep. Med. Chem. 39, 259–276.

    Article  CAS  Google Scholar 

  16. Anderson, A. C. (2003) The process of structure-based drug design. Chem. Biol. 10, 787–797.

    Article  PubMed  CAS  Google Scholar 

  17. Karp, P. D. (2001) Pathway databases: a case study in computational symbolic theories. Science 293, 2040–2044.

    Article  PubMed  CAS  Google Scholar 

  18. Edgar, R. C. and Kimmen, S. (2004) COACH: profile-profile alignment of roteins families using hidden Markov models. Bioinformatics, 20, 1309–1308.

    Article  PubMed  CAS  Google Scholar 

  19. Needleman, S. B. and Wunsch, C. D. (1970). A general method applicable to the search for similarities in the amino acid sequence of two proteins. J. Mol. Biol. 48, 443–453.

    Article  PubMed  CAS  Google Scholar 

  20. Kanehisa, M. (2000) Post-genome Informatics, Oxford University Press, New York.

    Google Scholar 

  21. Browne, W. J., North, A. C., Phillips, D. C., Drew, K., Vanaman, T. C. and Hill, R. L. (1969) A possible threedimensional structure of bovine alpha-lactalbumin based on that of hen’s egg-white lysozyme. J. Mol. Biol., 42, 65–86.

    Article  PubMed  CAS  Google Scholar 

  22. Sánchez, R. and Sali, A. (1999) ModBase: a database of comparative protein structure models. Bioinformatics 15, 1060–1061.

    Article  PubMed  Google Scholar 

  23. Gerstein, M. and Levitt, M. (1997) Structural census of the current population of protein sequences. Proc. Natl. Acad. Sci. U.S.A. 94, 11,911–11,916.

    Article  CAS  Google Scholar 

  24. Fischer, D. and Eisenberg, D. (1999) Predicting structures for genome proteins. Curr. Opin. Struct. Biol. 9, 208–211.

    Article  PubMed  CAS  Google Scholar 

  25. Uchoa, H. B., Jorge, G. E., da Silveira, N. J. F., Câmera, J. C., Jr., Canduri, F., and de Azevedo, W. F., Jr. (2004) Parmodel: a Web server for automated comparative modeling of proteins. Biochem. Biophys. Res. Commun. 325, 1481–1486.

    Article  PubMed  CAS  Google Scholar 

  26. MacKerell, A. D. J., Bashford, D., Bellott, R. L., et al. (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 102, 3586–3616.

    Article  CAS  Google Scholar 

  27. Laskowski, R. A., MacArthur, M. W., and Thornton, J. M. (1998) Validation of proteins derived from experiment. Curr. Opin. Struct. Biol. 8, 631–639.

    Article  PubMed  CAS  Google Scholar 

  28. Wilson, C., Gregoret, L. M., and Agard, D. A. (1993) Modeling side-chain conformation for homologous proteins using an energy-based rotamers search. J. Mol. Biol. 229, 996–1006.

    Article  PubMed  CAS  Google Scholar 

  29. Laskowski, R. A., MacArthurm, M. W., Smith, D. K., et al. (1994) PROCHECK v.3.0—program to check the stereochemistry quality of protein structures—operating instructions.

  30. Hooft, R. W., Sander, C., and Vriend, G. (1996) Positioning hydrogen atoms by optimizing hydrogen-bond networks in proteins structures. Proteins 26, 363–376.

    Article  PubMed  CAS  Google Scholar 

  31. Bowie, J. U., Luthy, R., and Eisenberg, D. (1991) A method to identify protein sequences that fold into a known three-dimensional structure. Science 253, 164–170.

    Article  PubMed  CAS  Google Scholar 

  32. Kabsch, W. and Sander, C. (1983) Dictionary of protein secondary structure: pattern recognition of hydrogenbonded and geometrical features. Biopolymers 22, 2577–2637.

    Article  PubMed  CAS  Google Scholar 

  33. Sippl, M. J. (1990) Calculation of conformational ensembles from potentials of mean force. An approach to the knowledge-based prediction of local structures in globular proteins. J. Mol. Biol. 213, 859–883.

    Article  PubMed  CAS  Google Scholar 

  34. Luthy, R., Bowie, J. U. and Eisenberg, K. (1992) Assessment of protein models with three-dimensional profiles. Nature 356, 83–85.

    Article  PubMed  CAS  Google Scholar 

  35. Arcuri, H. A., Canduri, F., Pereira, J. H., et al. (2004) Molecular models for shikimate pathway enzymes of Xylella fastidiosa. Biochem. Biophys. Res. Commun. 320, 979–991.

    Article  PubMed  CAS  Google Scholar 

  36. da Silveira, N. J. F., Uchoa, H. B., Canduri, F. et al. (2004) Structural bioinformatics study of PNP from Schistosoma mansoni. Biochem. Biophys. Res. Commun. 322, 100–104.

    Article  PubMed  Google Scholar 

  37. Brünger, A. T. (1992) X-PLOR, A System for Crystallography and NMR, Version 3.1, Yale University Press, New Haven, CT.

    Google Scholar 

  38. EU 3-D Validation Network (1998) Who checks the checkers? Four validation tools applied to eight atomic resolution structures. J. Mol. Biol. 276, 417–436.

    Article  Google Scholar 

  39. DuBois, P. (2000) MySQL, New Riders, Indianapolis, IN.

    Google Scholar 

  40. Pieper, U., Eswar, N., Braberg, H., et al. (2004) MODBASE, a database of annotated comparative protein structure models, and associated resources. Nucleic Acids Res. 32, D217-D222.

    Article  PubMed  CAS  Google Scholar 

  41. Kawabata, T., Fukuchi, S., Homma, K., et al. (2002) GTOP: a database of protein structures predicted from genome sequences. Nucleic Acids Res. 30, 294–298.

    Article  PubMed  CAS  Google Scholar 

  42. Ogata, H., Goto, S., Sato, K., Fujibuchi, W., Bono, H., and Kanehisa, M. (1999) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 27, 29–34.

    Article  PubMed  CAS  Google Scholar 

  43. Karp, P. D., Riley, M., Paley, S. M. and Pellegrini-Toole, A. (2002) The MetaCyc Database. Nucleic Acids Res. 30, 59–61.

    Article  PubMed  CAS  Google Scholar 

  44. Coggins, J. R., Abell, C., Evans, L. B., et al. (2003) Experiences with the shikimate-pathway enzymes as targets for rational drug design. Biochem. Soc. Trans. 31, 548–552.

    Article  PubMed  CAS  Google Scholar 

  45. Campbell, S. A., Richards, T. A., Mui, E. J., et al. (2004) A complete shikimate pathway in Toxoplasma gondii: an ancient eukaryotic innovation. Int. J. Parasitol. 34, 5–13.

    Article  PubMed  CAS  Google Scholar 

  46. Herman, K. M. and Weaver, L. M. (1999) The shikimate pathway. Annu. Rev. Plant Mol. Biol. 50, 473–503.

    Article  Google Scholar 

  47. de Azevedo, W. F., Jr., Canduri, F., de Oliveira, J. S., et al. (2002) Molecular model of shikimate kinase from Mycobacterium tuberculosis. Biochem. Biophys. Res. Commun. 295, 142–148.

    Article  Google Scholar 

  48. Pereira, J. H., Canduri, F., de Oliveira, J. S., et al. (2003) Structural bioinformatics study of EPSP synthase from Mycobacterium tuberculosis. Biochem. Biophys. Res. Commun. 312, 608–614.

    Article  PubMed  CAS  Google Scholar 

  49. Pereira, J. H., Oliveira, J. S., Canduri, F. et al. (2004) Structure of shikimate kinase from Mycobacterium tuberculosis reveals the binding of shikimic acid. Acta Crystallogr. D. Biol. Crystallogr. 60, 2310–2319.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Departamento de Fisica, Programa de Pós-graduação em Biofisica Molecular UNESP, São José do Rio Preto, SP, Brazil

    Nelson José Freitas da Silveira, Carlos Eduardo Bonalumi, Hugo Brandão Uchôa & José Henrique Pereira

  2. Departmento de Morfofisiologia-CCBS-UFMS, 79070-900, Campo Grande-MS, Brazil

    Fernanda Canduri

  3. Faculdade de Biociências-PUCRS, 90619-900, Porto Alegre-RS, Brazil

    Walter Filgueira de Azevedo Jr.

Authors
  1. Nelson José Freitas da Silveira
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  2. Carlos Eduardo Bonalumi
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  3. Hugo Brandão Uchôa
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  4. José Henrique Pereira
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  5. Fernanda Canduri
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  6. Walter Filgueira de Azevedo Jr.
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Correspondence to Walter Filgueira de Azevedo Jr..

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da Silveira, N.J.F., Bonalumi, C.E., Uchôa, H.B. et al. Dbmodeling. Cell Biochem Biophys 44, 366–374 (2006). https://doi.org/10.1385/CBB:44:3:366

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