Abstract
The goal of this work was to propose a possible mechanism for the butyrylcholinesterase activation by 2,4,6-trinitrotoluene (TNT), 3,3-dimethylbutyl-N-n-butylcarbamate (1), and 2-trimethylsilyl-ethyl-N-n-butylcarbamate (2). Kinetically, TNT, and compounds 1 and 2 were characterized as the nonessential activators of butyrylcholinesterase. TNT, and compounds 1 and 2 were hydrophobic compounds and were proposed to bind to the hydrophobic activator binding site, which was located outside the active site gorge of the enzyme. The conformational change from a normal active site gorge to a more accessible active site gorge of the enzyme was proposed after binding of TNT, and compounds 1 and 2 to the activator binding site of the enzyme. Therefore, TNT, and compounds 1 and 2 may act as the excess of butyrylcholine in the substrate activator for the butyrylcholinesterase catalyzed reactions.
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Massoulie, J., Pezzementi, L., Bon, S., Krejci, E., & Vallette, F. M. (1993). Progress in Neurobiology, 41, 31–91.
Xie, W.-H., Stribley, J. A., Chatonnet, A., Wilder, P. J., Rizzino, A., & McComb, R. D. (2000). Journal of Pharmacology and Experimental Therapeutics, 293, 869–902.
Giacobini, E. (2003). Butyrylcholinesterase: Its function and inhibitors. New York: Martin Dunitz.
Cokugras, A. E. (2003). Turkish Journal of Biochemistry, 28, 54–61.
Zhan, C.-G., Zheng, F., & Landry, D. W. (2003). Journal of the American Chemical Society, 125, 2462–2474.
Nicolet, Y., Lockridge, O., Masson, P., Fntecilla-Camps, J. C., & Nachon, F. (2003). Journal of Biological Chemistry, 287, 41141–41147.
Loudwig, S., Nicolet, Y., Masson, P., Fontecilla-Camps, J. C., Bon, S., & Nachon, F. (2003). ChemBioChem, 4, 762–767.
Quinn, D. M. (1987). Chemical Reviews, 87, 955–979.
Sussman, J. L., Harel, M., Frolow, F., Oefner, C., Goldman, A., & Toker, L. (1991). Science, 253, 872–879.
Harel, M., Schalk, I., Ehret-Sabatier, L., Bouet, F., Goeldner, M., & Hirth, L. (1993). Proceedings of the National Academy of Sciences of the United States of America, 90, 9031–9035.
Harel, M., Quinn, D. M., Nair, H. K., Silman, I., & Sussman, J. L. (1996). Journal of the American Chemical Society, 118, 2340–2346.
Savini, L., Gaeta, A., Fattorusso, C., Catalanotti, B., Campiani, G., & Chiasserini, L. (2003). Journal of Medicinal Chemistry, 46, 1–4.
Masson, P., Xie, W., Forment, M.-T., Levitsky, V., Fortier, P.-L., & Albaret, C. (1999). Biochimica et Biophysica Acta, 1433, 281–293.
Lin, G., Tsai, H.-J., & Tsai, Y.-H. (2003). Bioorganic & Medicinal Chemistry Letters, 13, 2887–2890.
Taylor, P., & Radic, Z. (1994). Annual Review of Pharmacology and Toxicology, 34, 281–320.
Tormos, J. R., Wiley, K. L., Seravalli, J., Nachon, F., Masson, P., & Nicolet, Y. (2005). Journal of the American Chemical Society, 127, 14538–14539.
Lothrop, W. C., & Handrick, G. R. (1949). Chemical Reviews, 44, 419–445.
Lin, M.-C., Hsieh, C.-W., Tsai, H.-J., Ro, Y.-R., Lin, C.-S., & Lin, G. (1998). Asian Journal of Chemistry, 20, 1217–1225.
Ellman, C. L., Courtney, K. D., Andres, V. J., & Featherstone, R. M. (1961). Biochemical Pharmacology, 7, 88–95.
Segel, I. H. (1975). Enzyme kinetics. New York: Wiley.
Cavalier, J.-F., Buono, G., & Verger, R. (2000). Accounts of Chemical Research, 33, 579–589.
Lin, M.-C., Lu, C.-P., Cheng, Y.-R., Lin, Y.-F., Lin, C.-S., & Lin, G. (2007). Chemistry and Physics of Lipids, 146, 85–93.
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We thank the National Science Council of Taiwan for financial support.
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Chiou, SY., Wu, YG. & Lin, G. Activation Mechanisms of Butyrylcholinesterase by 2,4,6-Trinitrotoluene, 3,3-Dimethylbutyl-N-n-butylcarbamate, and 2-Trimethylsilyl-ethyl-N-n-butylcarbamate. Appl Biochem Biotechnol 150, 337–344 (2008). https://doi.org/10.1007/s12010-008-8295-z
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DOI: https://doi.org/10.1007/s12010-008-8295-z