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Conformational changes of peptidoglycan fragments during their interactions with vancomycin

  • Research Article
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Central European Journal of Chemistry

Abstract

Six complexes of vancomycin and peptidoglycan precursors were studied via molecular dynamics simulations. The interactions between the antibiotic and peptidoglycan fragments were identified and described in detail. All six studied modifications of the peptidoglycan precursor resulted in a weakening of the interaction with vancomycin when comparing to the native D-Ala-D-Ala-terminated fragment. It was confirmed that the N-terminus of the vancomycin is directly responsible for peptidoglycan recognition and antimicrobial activity. In simulated systems, the saccharide part of the antibiotic interacts with peptide precursors, thus it could also be important for antimicrobial activity. The complex terminated with D-Lac is the only one in which there is a weak interaction with the sugar moiety in the simulated systems. Analysis of conformational changes is a major scope of this work. The lack of interactions resulting from modification of the peptidoglycan precursors (D-Lac, D-Ser or other substitution) would be counterbalanced by proper modifications of the vancomycin moiety, especially the saccharide part of vancomycin.

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References

  1. D. Kahne, C. Leimkuhler, W. Lu, C. Walsh, Chem. Rev. 105, 425 (2005)

    Article  CAS  Google Scholar 

  2. D.H. Williams, B. Bardsley, Angew. Chem. Int. Ed. 38, 1172 (1999)

    Article  Google Scholar 

  3. P.E. Reynolds, Eur. J. Clin. Microbiol. Infect. Dis. 8, 943 (1989)

    Article  CAS  Google Scholar 

  4. M. Arthur, P. Reynolds, P. Courvalin, Trends Microbiol. 4, 401 (1996)

    Article  CAS  Google Scholar 

  5. M. Fines, B. Périchon, P. Reynolds, D.F. Sahm, P. Courvalin, Antimicrob. Agents Chemother. 43, 2161 (1999)

    CAS  Google Scholar 

  6. R. Leclercq, S. Dutka-Malen, J. Duval, P. Courvalin, Antimicrob. Agents Chemother. 36, 2005 (1992)

    CAS  Google Scholar 

  7. S.J. McKessar, A.M. Berry, J.M. Bell, J.D. Turnidge, J.C. Paton, Antimicrob. Agents Chemother. 44, 3224 (2000)

    Article  CAS  Google Scholar 

  8. F. Navarro, P. Courvalin, Antimicrob. Agents Chemother. 38, 1788 (1994)

    CAS  Google Scholar 

  9. B. Périchon, P. Reynolds, P. Courvalin, Antimicrob. Agents Chemother. 41, 2016 (1997)

    Google Scholar 

  10. T.D.H. Bugg, G.D. Wright, S. Dutka-Malen, M. Arthur, P. Courvalin, C.T. Walsh, Biochemistry 30, 10408 (1991)

    Article  CAS  Google Scholar 

  11. P.E. Reynolds, P. Courvalin, Antimicrob. Agents Chemother. 49, 21 (2005)

    Article  CAS  Google Scholar 

  12. M. Arthur, P. Courvalin, Antimicrob. Agents Chemother. 37, 1563 (1993)

    CAS  Google Scholar 

  13. D.P. Levine, Clin. Infect. Dis. 42Suppl. 1, 5 (2006)

    Article  Google Scholar 

  14. C.T. Walsh, S.L. Fisher, I.-S. Park, M. Prahalad, Z. Wu, Chem. Biol. 3, 21 (1996)

    Article  CAS  Google Scholar 

  15. D. Billot-Klein, L. Gutmann, S. Sable, E. Guitet, J. van Heijenoort, J. Bacteriol. 176, 2398 (1994)

    CAS  Google Scholar 

  16. P.E. Reynolds, H.A. Snaith, A.J. Maguire, S. Dutka-Malen, P. Courvalin, Biochem. J. 301, 5 (1994)

    CAS  Google Scholar 

  17. J.C. Barna, D.H. Wiliams, Annu. Rev. Microbiol. 38, 339 (1984)

    Article  CAS  Google Scholar 

  18. R. Kannan, C.M. Harris, T.M. Harris, J.P. Waltho, N.J. Skelton, D.H. Williams, J. Am. Chem. Soc. 110, 2946 (1988)

    Article  CAS  Google Scholar 

  19. J.P. Waltho, D.H. Williams, D.J.H. Stone, N.J. Skelton, J. Am. Chem. Soc. 110, 5638 (1988)

    Article  CAS  Google Scholar 

  20. D.A. Beauregard, D.H. Williams, M.N. Gwynn, D.J.C. Knowles, Antimicrob. Agents Chemother. 39, 781 (1995)

    CAS  Google Scholar 

  21. P. Groves, M.S. Searle, J.P. MacKay, D.H. Williams, Structure 2, 747 (1994)

    Article  CAS  Google Scholar 

  22. J.-G. Lee, C. Sagui, C. Roland, Int. J. Quantum Chem. 110, 2894 (2010)

    Article  CAS  Google Scholar 

  23. J.P. MacKay, U. Gerhard, D.A. Beauregard, M.S. Westweil, M.S. Searle, D.H. Williams, J. Am. Chem. Soc. 116, 4581 (1994)

    Article  CAS  Google Scholar 

  24. P.J. Loll, A.E. Bevivino, B.D. Korty, P.H. Axelsen, J. Am. Chem. Soc. 119, 1516 (1997)

    Article  CAS  Google Scholar 

  25. D.A. Case, T.A. Darden, T.E. III Cheatham, C.L. Simmerling, J. Wang, R.E. Duke, R. Luo, K.M. Merz, D.A. Pearlman, M. Crowley, R.C. Walker, W. Zhang, B. Wang, S. Hayik, A. Roitberg, G. Seabra, K.F. Wong, F. Paesani, X. Wu, S. Brozell, V. Tsui, H. Gohlke, L. Yang, C. Tan, J. Mongan, V. Hornak, G. Cui, P. Beroza, D.H. Mathews, C. Schafmeister, W.S. Ross, P.A. Kollman, AMBER 9 (University of California, San Francisco, 2006)

    Google Scholar 

  26. M Basma, S. Sundara, D. Calgan, T. Venali, R.J. Woods, J. Comput. Chem. 22, 1125 (2001)

    Article  CAS  Google Scholar 

  27. K.N. Kirschner, R.J. Woods, Proc. Natl. Acad. Sci. USA 98, 10541 (2001)

    Article  CAS  Google Scholar 

  28. Y. Duan, C. Wu, S. Chowdhury, M.C. Lee, G. Xiong, W. Zhang, R. Yang, P. Cieplak, R. Luo, T. Lee, J. Comput. Chem. 24, 1999 (2003)

    Article  CAS  Google Scholar 

  29. M.W. Schmidt, K.K. Baldridge, J.A. Boatz, S.T. Elbert, M.S. Gordon, J.H. Jensen, S. Koseki, N. Matsunaga, K.A. Nguyen, S. Su, T.L. Windus, M. Dupuis, J.A. Montgomery, J. Comput. Chem. 14, 1347 (1993)

    Article  CAS  Google Scholar 

  30. C.L. Bayly, P. Cieplak, W.D. Cornell, P.A. Kollman, J. Phys. Chem. 97, 10269 (1993)

    Article  CAS  Google Scholar 

  31. Y. Nitanai, K. Kakoi, K. Aoki, PDB accession code 1FVM (2000), DOI: 10.2210/pdb1fvm/pdb

  32. V. Tsui, D.A. Case, Biopol. Nucl. Acid. Sci. 56, 275 (2001)

    CAS  Google Scholar 

  33. C.P. Sosa, T. Hewitt, M.S. Lee, D.A. Case, J. Mol. Struct. (Theochem) 549, 193 (2001)

    Article  CAS  Google Scholar 

  34. P.A. Kollman, I. Massova, C. Reyes, B. Kuhn, B.S. Huo, L. Chong, M. Lee, T. Lee, Y. Duan, W. Wang, O. Donini, P. Cieplak, J. Srinivasan, D.A. Case, T.E. Cheatham, Acc. Chem. Res. 33, 889 (2000)

    Article  CAS  Google Scholar 

  35. S.S. Leung, J. Tirado-Rives, W.L. Jorgensen, Bioorg. Med. Chem. Lett. 19, 1236 (2009)

    Article  CAS  Google Scholar 

  36. S.S. Leung, J. Tirado-Rives, W.L. Jorgensen, Bioorg. Med. Chem. 17, 5874 (2009)

    Article  CAS  Google Scholar 

  37. Z. Yang, E.R. Vorpagel, J. Laskin, J. Am. Chem. Soc. 130, 13013 (2008)

    Article  CAS  Google Scholar 

  38. D. Billot-Klein, D. Blanot, L. Gutmann, J. van Heijenoort, Biochem. J. 304, 1021 (1994)

    CAS  Google Scholar 

  39. M. Batchelor, D. Zhou, M.A. Cooper, C. Abell, T. Rayment, Org. Biomol. Chem. 8, 142 (2010)

    Article  Google Scholar 

  40. J.B. Hamburger, A.J. Hoertz, A. Lee, R.J. Senturia, D.G. McCafferty, P.J. Loll, Proc. Natl. Acad. Sci. USA 106, 13759 (2009)

    Article  CAS  Google Scholar 

  41. B. Périchon, P. Courvalin, Antimicrob. Agents Chemother. 53, 4580 (2009)

    Article  Google Scholar 

  42. J.C. Poully, F. Lecomte, N. Nieuwjaer, B. Manil, J.P. Schermann, C. Desfrançois, F. Calvo, G. Grégoire, Phys. Chem. Chem. Phys. 12, 3606 (2010)

    Article  CAS  Google Scholar 

  43. Z. Yang, E.R. Vorpagel, J. Laskin, Chem. Eur. J. 15, 2081 (2009)

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Faculty of Chemistry, University of Gdańsk, 80-952, Gdańsk, Poland

    Rafał Ślusarz, Magdalena J. Ślusarz, Justyna Samaszko & Janusz Madaj

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  1. Rafał Ślusarz
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  2. Magdalena J. Ślusarz
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  3. Justyna Samaszko
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  4. Janusz Madaj
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Correspondence to Rafał Ślusarz.

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Ślusarz, R., Ślusarz, M.J., Samaszko, J. et al. Conformational changes of peptidoglycan fragments during their interactions with vancomycin. cent.eur.j.chem. 9, 422–431 (2011). https://doi.org/10.2478/s11532-011-0015-9

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