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Molecular modeling of butyrylcholinesterase inhibition by cresyl saligenin phosphate

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Abstract

Presumably, aerotoxic syndrome is caused by the impact of tricresyl phosphate (TCP), a lubricating oil additive for aircraft engines, on the human body. The most toxic tri-ortho-isomer of this compound is metabolized in the body to give cresyl saligenin phosphate (CSP), which inhibits butyrylcholinesterase (BChE) giving phosphoserine. In this case, BChE acts as a stoichiometric bioscavenger irreversibly binding CSP and as a biomarker of exposure to low doses of TCP. The mechanism of CSP interaction with BChE at the initial stage of formation of the enzyme—inhibitor complex was studied by molecular modeling techniques. The results indicate that BChE interaction with the (R)-enantiomer of CSP in the most stable envelope conformation of the saligenin ring is most preferable. Comparison of the results obtained using different computation methods demonstrated that the best agreement with experimental data can be achieved by combining standard molecular docking methods with quantum mechanics methods for more accurate structure preparation.

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References

  1. C. Winder, Curr. Top. Toxicol., 2006, 3, 65.

    Google Scholar 

  2. C. Winder, J.-C. Balouet, Environ. Res., 2002, 89, 146.

    Article  CAS  Google Scholar 

  3. G. De Nola, J. Kibby, W. Mazurek, J. Chromatogr. A, 2008, 1200, 211.

    Article  Google Scholar 

  4. M. Eto, J. E. Casida, T. Eto, Biochem. Pharmacol., 1962, 11, 337.

    Article  CAS  Google Scholar 

  5. D. M. Maxwell, Toxicol. Appl. Pharmacol., 1992, 114, 306.

    Article  CAS  Google Scholar 

  6. J. E. Casida, G. B. Quistad, Chem. Res. Toxicol., 2004, 17, 983.

    Article  CAS  Google Scholar 

  7. L. M. Schopfer, C. E. Furlong, O. Lockridge, Anal. Biochem., 2010, 404, 64.

    Article  CAS  Google Scholar 

  8. E. Carletti, J.-P. Colletier, L. M. Schopfer, G. Santoni, P. Masson, O. Lockridge, F. Nachon, M. Weik, Chem. Res. Toxicol., 2013, 26, 280.

    Article  CAS  Google Scholar 

  9. G. P. Moss, Pure Appl. Chem., 1996, 68, 2193.

    Article  CAS  Google Scholar 

  10. E. Carletti, L. M. Schopfer, J.-P. Colletier, M. T. Froment, F. Nachon, M. Weik, O. Lockridge, P. Masson, Chem. Res. Toxicol., 2011, 24, 797.

    Article  CAS  Google Scholar 

  11. H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, P. E. Bourne, Nucl. Acids Res., 2000, 28, 235.

    Article  CAS  Google Scholar 

  12. 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. J. Su, T. L. Windus, M. Dupuis, J. A. Montgomery, J. Comput. Chem., 1993, 14, 1347.

    Article  CAS  Google Scholar 

  13. A. D. Becke, J. Chem. Phys., 1993, 98, 5648.

    Article  CAS  Google Scholar 

  14. J. P. Stewart, J. Mol. Model., 2007, 13, 1173.

    Article  CAS  Google Scholar 

  15. J. P. Stewart, J. Mol. Model., 2013, 19, 1.

    Article  CAS  Google Scholar 

  16. J. J. P. Stewart, MOPAC2012, Stewart Computational Chemistry, Colorado Springs, CO, USA; http://OpenMOPAC.net.

  17. A. Pedretti, L. Villa, G. Vistoli, J. Comp.-Aided Mol. Des., 2004, 18, 167.

    Article  CAS  Google Scholar 

  18. A. Hocquet, M. Langgerd, J. Mol. Model., 1998, 4, 94.

    Article  CAS  Google Scholar 

  19. N. O’boyle, M. Banck, C. James, C. Morley, T. Vandermeersch, G. Hutchison, J. Cheminform., 2011, 3, 33.

    Article  Google Scholar 

  20. G. M. Morris, R. Huey, W. Lindstrom, M. F. Sanner, R. K. Belew, D. S. Goodsell, A. J. Olson, J. Comput. Chem., 2009, 30, 2785.

    Article  CAS  Google Scholar 

  21. G. M. Morris, D. S. Goodsell, R. S. Halliday, R. Huey, W. E. Hart, R. K. Belew, A. J. Olson, J. Am. Chem. Soc., 1998, 19, 1639.

    CAS  Google Scholar 

  22. J. Gasteiger, M. Marsili, Tetrahedron Lett., 1978, 19, 3181.

    Article  Google Scholar 

  23. R. S. Mulliken, J. Chem. Phys., 1955, 23, 1833.

    Article  CAS  Google Scholar 

  24. P.-O. Löwdin, in Advances in Quantum Chemistry, Ed. L. Per-Olov, Academic Press, 1970, c. 185.

  25. Y. Nicolet, O. Lockridge, P. Masson, J. C. Fontecilla-Camps, F. Nachon, J. Biol. Chem., 2003, 278, 41141.

    Article  CAS  Google Scholar 

  26. J. M. Word, S.C. Lovell, J. S. Richardson, D. C. Richardson, J. Mol. Biol., 1999, 285, 1735.

    Article  CAS  Google Scholar 

  27. P. Masson, S. Lushchekina, L. M. Schopfer, O. Lockride, Biochem. J., 2013, 454, 387.

    Article  CAS  Google Scholar 

  28. J. C. Phillips, R. Braun, W. Wang, J. Gumbart, E. Tajkhorshid, E. Villa, C. Chipot, R. D. Skeel, L. Kalé, K. Schulten, J. Comput. Chem., 2005, 26, 1781.

    Article  CAS  Google Scholar 

  29. R. B. Best, X. Zhu, J. Shim, P. E. M. Lopes, J. Mittal, M. Feig, A. D. Mackerell, J. Chem. Theory Comput., 2012, 8, 3257.

    Article  CAS  Google Scholar 

  30. E. J. Bylaska, W. A. De Jong, N. Govind, K. Kowalski, T. P. Straatsma, M. Valiev, D. Wang, E. Apra, T. L. Windus, J. Hammond, P. Nichols, S. Hirata, M. T. Hackler, Y. Zhao, P.-D. Fan, R. J. Harrison, M. Dupuis, D. M. A. Smith, J. Nieplocha, V. Tipparaju, M. Krishnan, A. Vazquez-Mayagoitia, Q. Wu, T. V. Voorhis, A. A. Auer, M. Nooijen, L. D. Crosby, E. Brown, G. Cisneros, G. I. Fann, H. Fruchtl, J. Garza, K. Hirao, R. Kendall, J. A. Nichols, K. Tsemekhman, K. Wolinski, J. Anchell, D. Bernholdt, P. Borowski, T. Clark, D. Clerc, H. Dachsel, M. Deegan, K. Dyall, D. Elwood, E. Glendening, M. Gutowski, A. Hess, J. Jaffe, B. Johnson, J. Ju, R. Kobayashi, R. Kutteh, Z. Lin, R. Littlefield, X. Long, B. Meng, T. Nakajima, S. Niu, L. Pollack, M. Rosing, G. Sandrone, M. Stave, H. Taylor, G. Thomas, J. Van Lenthe, A. Wong, Z. Zhang, A Computational Chemistry Package for Parallel Computers, NWChem, 2009.

    Google Scholar 

  31. V. Sadovnichy, A. Tikhonravov, V. Voevodin, and V. Opanasenko, in Contemporary High Performance Computing: From Petascale toward Exascale (Chapman & Hall/CRC Computational Science), CRC Press, Boca Raton, USA 2013, p. 283.

    Google Scholar 

  32. F. Nachon, O. A. Asojo, G. E. Borgstahl, P. Masson, O. Lockridge, Biochemistry, 2005, 44, 1154.

    Article  CAS  Google Scholar 

  33. K. A. Petrov, L. O. Yagodinal, G. R. Valeeva, N. I. Lannik, A. D. Nikitashina, A. A. Rizvanov, V. V. Zobov, E. A. Bukharaeva, V. S. Reznik, E. E. Nikolsky, F. Vyskoèil, Br. J. Pharmacol, 2011, 163, 732–744.

    Article  CAS  Google Scholar 

  34. A. R. Main, Science, 1964, 144, 992.

    Article  CAS  Google Scholar 

  35. O. Lockridge, R. M. Blong, P. Masson, M. T. Froment, C. B. Millard, C. A. Broomfield, Biochemistry, 1997, 36, 786.

    Article  CAS  Google Scholar 

  36. I. M. Kovach, J. Phys. Org. Chem., 2004, 17, 602.

    Article  CAS  Google Scholar 

  37. P.-C. Tsai, A. Bigley, Y. Li, E. Ghanem, C. L. Cadieux, S. A. Kasten, T. E. Reeves, D. M. Cerasoli, F. M. Raushel, Biochemistry, 2010, 49, 7978.

    Article  CAS  Google Scholar 

  38. F. Zheng, C. G. Zhan, Org. Biomol. Chem., 2008, 6, 836.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. N. M. Emanuel’ Institute of Biochemical Physics, Russian Academy of Sciences, 4 ul. Kosygina, 119334, Moscow, Russian Federation

    S. V. Lushchekina & S. D. Varfolomeev

  2. Department of Chemistry, M.V. Lomonosov Moscow State University, 1/3 Leninskie gory, 119991, Moscow, Russian Federation

    V. S. Polomskikh & S. D. Varfolomeev

  3. Institute of Structural Biology, 38027, Grenoble Cedex, France

    P. Masson

  4. University of Nebraska Medical Center, Eppley Institute, Omaha, NE, 68198-5950, USA

    P. Masson

Authors
  1. S. V. Lushchekina
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  2. V. S. Polomskikh
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  3. S. D. Varfolomeev
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  4. P. Masson
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Correspondence to S. V. Lushchekina.

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Dedicated to Academician of the Russian Academy of Sciences M. P. Egorov on the occasion of his 60th birthday.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2527–2537, Novemer, 2013.

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Lushchekina, S.V., Polomskikh, V.S., Varfolomeev, S.D. et al. Molecular modeling of butyrylcholinesterase inhibition by cresyl saligenin phosphate. Russ Chem Bull 62, 2527–2537 (2013). https://doi.org/10.1007/s11172-013-0366-9

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  • DOI: https://doi.org/10.1007/s11172-013-0366-9

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