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Bioinorganic Reaction Mechanisms—Quantum Chemistry Approach

  • Tomasz BorowskiEmail author
  • Ewa BroclawikEmail author
Chapter
Part of the Springer Series on Bio- and Neurosystems book series (SSBN, volume 8)

Abstract

This chapter is focused on applications of quantum chemical (QC) DFT methodology to study reaction mechanisms of metalloenzymes, emphasising new insights that could be obtained thanks to the computations and showing the limitations of the QC approach. Several case studies taken from Authors’ research serve to explain and rationalize modelling protocols and to underline information provided by computations, which are not accessible from experiment. Case studies are assorted as to illustrate how the most likely mechanisms may be identified among mechanistic proposals. It is also highlighted how deliberate model constructing and probing various scenarios and/or electronic states help in identifying key factors ruling enzymatic reactions. It is hoped this contribution clarified that credibility of the results relies heavily on chemical knowledge, intuition as well as on experience of the researcher.

Notes

Acknowledgements

This research project was supported by grant No. UMO-2011/01/B/ST4/02620 from the National Science Centre, Poland, and partly supported by grants: POKL.04.0101-00-434/08-00, 2011/01/N/ST4/02330 and, Kraków Interdisciplinary Ph.D.-Project in Nanoscience and Advanced Nanostructures” operated within the Foundation for Polish Science MPD Programme co-financed by the EU European Regional Development Fund.

References

  1. 1.
    Antosiewicz, J., Shugar, D.: Poisson–Boltzmann continuum-solvation models: applications to pH-dependent properties of biomolecules. Mol. Biosyst. 7, 2923–2949 (2011)CrossRefGoogle Scholar
  2. 2.
    Becke, A.D.J.: Density-functional thermochemistry. III. The role of exact exchange. Chem. Phys. 98, 5648–5652 (1993)Google Scholar
  3. 3.
    Blomberg, M.R.A., Siegbahn, P.E.M.: A quantum chemical approach to the study of reaction mechanisms of redox-active metalloenzymes. J. Phys. Chem. B 105, 9375–9386 (2001).  https://doi.org/10.1021/jp010305fCrossRefGoogle Scholar
  4. 4.
    Borowski, T., Bassan, A., Siegbahn, P.E.M.: 4-Hydroxyphenylpyruvate dioxygenase: a hybrid density functional study of the catalytic reaction mechanism. Biochemistry 43, 12,331–12,342 (2004)CrossRefGoogle Scholar
  5. 5.
    Borowski, T., Bassan, A., Siegbahn, P.E.M.: Mechanism of dioxygen activation in 2-oxoglutarate-dependent enzymes: a hybrid DFT study. Chem. Eur. J. 10(4), 1031–1041 (2004).  https://doi.org/10.1002/chem.200305306CrossRefGoogle Scholar
  6. 6.
    Borowski, T., Georgiev, V., Siegbahn, P.E.M.: On the observation of a gem diol intermediate after O–O bond cleavage by extradiol dioxygenases: a hybrid DFT study. J. Mol. Model 16(11), 1673–1677 (2010).  https://doi.org/10.1007/s00894-010-0652-5CrossRefGoogle Scholar
  7. 7.
    Borowski, T., Noack, H., Radoń, M., Zych, K., Siegbahn, P.E.M.: Mechanism of selective halogenation by SyrB2: a computational study. J. Am. Chem. Soc. 132(37), 12887–12898 (2010b).  https://doi.org/10.1021/ja101877aCrossRefGoogle Scholar
  8. 8.
    Borowski, T., Wójcik, A., Miłaczewska, A., Georgiev, V., Blomberg, M.R.A., Siegbahn, P.E.M.: The alkenyl migration mechanism catalyzed by extradiol dioxygenases: a hybrid DFT study. J. Biol. Inorg. Chem. (2012).  https://doi.org/10.1007/s00775-012-0904-1CrossRefGoogle Scholar
  9. 9.
    Brownlee, J., He, P., Moran, G.R., Harrison, D.H.T.: Two roads diverged: the structure of hydroxymandelate synthase from Amycolatopsis orientalis in complex with 4-hydroxymandelate. Biochemistry 47(7), 2002–2013 (2008).  https://doi.org/10.1021/bi701438rCrossRefGoogle Scholar
  10. 10.
    Bugg, T.D., Sanvoisin, J., Spence, E.L.: Exploring the catalytic mechanism of the extradiol catechol dioxygenases. Biochem. Soc. Trans. 25(1), 81–85 (1997)CrossRefGoogle Scholar
  11. 11.
    Burzlaff, N.I., Rutledge, P.J., Clifton, I.J., Hensgens, C.M., Pickford, M., Adlington, R.M., Roach, P.L., Baldwin, J.E.: The reaction cycle of isopenicillin N synthase observed by X-ray diffraction. Nature 401(6754), 721–724 (1999).  https://doi.org/10.1038/44400CrossRefGoogle Scholar
  12. 12.
    Dann, C.E., Bruick, R.K., Deisenhofer, J.: Structure of factor-inhibiting hypoxia-inducible factor 1: an asparaginyl hydroxylase involved in the hypoxic response pathway. Proc. Nat. Acad. Sci. U.S.A 99(24), 15,351–15,356 (2002).  https://doi.org/10.1073/pnas.202614999CrossRefGoogle Scholar
  13. 13.
    Dellago, C., Bolhuis, P.G.: Transition path sampling simulations of biological systems. Top. Curr. Chem. 268, 291–317 (2007)CrossRefGoogle Scholar
  14. 14.
    Evans, D.A., Wales, D.J.: Free energy landscapes of model peptides and proteins. J. Chem. Phys. 118, 3891 (2003)CrossRefGoogle Scholar
  15. 15.
    Flashman, E., Schofield, C.J.: The most versatile of all reactive intermediates? Nat. Chem. Biol. 3(2), 86–87 (2007).  https://doi.org/10.1038/nchembio0207-86CrossRefGoogle Scholar
  16. 16.
    Georgiev, V., Borowski, T., Blomberg, M.R.A., Siegbahn, P.E.M.: A compartison of the reaction mechanisms of iron- and manganese-containing 2,3-HPCD: an important spin transition for manganese. J. Biol. Inorg. Chem. 13, 929–940 (2008)CrossRefGoogle Scholar
  17. 17.
    Georgieva, P., Himo, F.: Quantum chemical modeling of enzymatic reactions: the case of histone lysine methyltransferase. J. Comput. Chem. 31(8), 1707–1714 (2010).  https://doi.org/10.1002/jcc.21458CrossRefGoogle Scholar
  18. 18.
    Grimme, S.: Semiempirical GGA-type density functional constructed with a long-range dispersion correction. J. Comput. Chem. 27, 1787–1799 (2006)CrossRefGoogle Scholar
  19. 19.
    Hammes-Schiffer, S.: Theory of proton-coupled electron transfer in energy conversion processes. Acc. Chem. Res. 42, 1881–1889 (2009)CrossRefGoogle Scholar
  20. 20.
    Hanauske-Abel, H.M., Gnzler, V.: A stereochemical concept for the catalytic mechanism of prolylhydroxylase: applicability to classification and design of inhibitors. J. Theor. Biol. 94(2), 421–455 (1982)CrossRefGoogle Scholar
  21. 21.
    Harvey, J.N., Aschi, M., Schwarz, H., Koch, W.: The singlet and triplet states of phenyl cation. A hybrid approach for locating minimum energy crossing points between non-interacting potential energy surfaces. Theor. Chem. Acc. 99, 95–99 (1998)CrossRefGoogle Scholar
  22. 22.
    Hausinger, R.P.: Fe(II)/\(\alpha \)-ketoglutarate-dependent hydroxylases and related enzymes. Crit. Rev. Biochem. Mol. Biol. 39(1), 21–68 (2004).  https://doi.org/10.1080/10409230490440541CrossRefGoogle Scholar
  23. 23.
    Higgins, L.J., Yan, F., Liu, P., Liu, H., Drennan, C.L.: Structural insight into antibiotic fosfomycin biosynthesis by a mononuclear iron enzyme. Nature 437(7060), 838–844 (2005).  https://doi.org/10.1038/nature03924CrossRefGoogle Scholar
  24. 24.
    Holm, R.H., Kennepohl, P., Solomon, E.S.: Structural and functional aspects of metal sites in biology. Chem. Rev. 96, 2239–2314 (1996).  https://doi.org/10.1021/cr9500390CrossRefGoogle Scholar
  25. 25.
    Hu, H., Lu, Z., Parks, J., Burger, S., Yang, W.: Quantum mechanics/molecular mechanics minimum free-energy path for accurate reaction energetics in solution and enzymes: sequential sampling and optimization on the potential of mean force surface. J. Chem. Phys. 128(034), 105 (2008)Google Scholar
  26. 26.
    Kawatsu, T., Lundberg, M., Morokuma, K.: Protein free energy corrections in ONIOM QM: MM modeling: A case study for isopenicillin N synthase (IPNS). J. Chem. Theory Comput. 7, 390–401 (2011)CrossRefGoogle Scholar
  27. 27.
    Kovaleva, E.G., Lipscomb, J.D.: Intermediate in the O–O bond cleavage reaction of an extradiol dioxygenase. Biochemistry 47, 11168–11170 (2008)CrossRefGoogle Scholar
  28. 28.
    Lee, C., Yang, W., Parr, R.G.: Development of the Colle-Salvetti correlation energy formula into a functional of the electron density. Phys. Rev. B 37, 785–789 (1988)CrossRefGoogle Scholar
  29. 29.
    Liu, P., Murakami, K., Seki, T., He, X., Yeung, S.M., Kuzuyama, T., Seto, H., Liu, H.: Protein purification and function assignment of the epoxidase catalyzing the formation of fosfomycin. J. Am. Chem. Soc. 123(19), 4619–4620 (2001)CrossRefGoogle Scholar
  30. 30.
    Maeda, S., Ohno, K., Morokuma, K.: Exploring multiple potential energy surfaces: photochemistry of small carbonyl compounds. Adv. Phys. Chem. Article ID 268,124, 13 pages (2012)Google Scholar
  31. 31.
    Mendel, S., Arndt, A., Bugg, T.D.H.: Acid-base catalysis in the extradiol catechol dioxygenase reaction mechanism: site-directed mutagenesis of His-115 and His-179 in Escherichia coli 2,3-dihydroxyphenylpropionate 1,2-dioxygenase (MhpB). Biochemistry 43(42), 13390–13396 (2004).  https://doi.org/10.1021/bi048518tCrossRefGoogle Scholar
  32. 32.
    Miłaczewska, A., Broclawik, E., Borowski, T.L.: On the catalytic mechanism of (S)-2-hydroxypropylphosphonic acid epoxidase (HppE): a hybrid DFT study. Chem. Eur. J. (2012).  https://doi.org/10.1002/chem.201202825CrossRefGoogle Scholar
  33. 33.
    Moran, G.R.: 4-Hydroxyphenylpyruvate dioxygenase. Arch. Biochem. Biophys. 433(1), 117–128 (2005).  https://doi.org/10.1016/j.abb.2004.08.015CrossRefGoogle Scholar
  34. 34.
    Ng, S.S., Kavanagh, K.L., McDonough, M.A., Butler, D., Pilka, E.S., Lienard, B.M.R., Bray, J.E., Savitsky, P., Gileadi, O., von Delft, F., Rose, N.R., Offer, J., Scheinost, J.C., Borowski, T., Sundstrom, M., Schofield, C.J., Oppermann, U.: Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity. Nature 448(7149), 87–91 (2007).  https://doi.org/10.1038/nature05971CrossRefGoogle Scholar
  35. 35.
    Pelmenschikov, V., Blomberg, M., Siegbahn, P.E.: A theoretical study of the mechanism for peptide hydrolysis by thermolysin. J. Biol. Inorg. Chem. 7, 284–298 (2002)CrossRefGoogle Scholar
  36. 36.
    Rod, T., Ryde, U.: Accurate QM/MM free energy calculation of enzyme reactions: Methylation by catechol O-methyltransferase. J. Chem. Theory Comput. 1, 1240–1251 (2005)CrossRefGoogle Scholar
  37. 37.
    Schenk, G., Mitić, N., Gahan, L.R., Ollis, D.L., McGeary, R.P., Guddat, L.W.: Binuclear metallohydrolases: Complex mechanistic strategies for a simple chemical reaction. Acc. Chem. Res. (2012).  https://doi.org/10.1021/ar300067gCrossRefGoogle Scholar
  38. 38.
    Schofield, C., Zhang, Z.: Structural and mechanistic studies on 2-oxoglutarate-dependent oxygenases and related enzymes. Curr. Opin. Struct. Biol. 9(6), 722–731 (1999)CrossRefGoogle Scholar
  39. 39.
    Senn, H., Thiel, W.: QM/MM methods for biological systems. Top. Curr. Chem. 268, 173–290 (2007)CrossRefGoogle Scholar
  40. 40.
    Sheppard, D., Terrell, R., Henkelman, G.: Optimization methods for finding minimum energy paths. J. Chem. Phys. 128(134), 106 (2008)Google Scholar
  41. 41.
    Siegbahn, P.E.M.: Modeling aspects of mechanisms for reactions catalyzed by metalloenzymes. J. Comput. Chem. 22, 1634–1645 (2001)CrossRefGoogle Scholar
  42. 42.
    Siegbahn, P.E.M.: Mechanisms of metalloenzymes studied by quantum chemical methods. Q. Rev. Biophys. 36, 91–145 (2003)CrossRefGoogle Scholar
  43. 43.
    Siegbahn, P.E.M., Borowski, T.: Modeling enzymatic reactions involving transition metals. Acc. Chem. Res. 39(10), 729–738 (2006).  https://doi.org/10.1021/ar050123uCrossRefGoogle Scholar
  44. 44.
    Siegbahn, P.E.M., Haeffner, F.: Mechanism for catechol ring-cleavage by non-heme iron extradiol dioxygenases. J. Am. Chem. Soc. 126(29), 8919–8932 (2004).  https://doi.org/10.1021/ja0493805CrossRefGoogle Scholar
  45. 45.
    Siegbahn, P.E.M., Himo, F.: Recent developments of the quantum chemical cluster approach for modeling enzyme reactions. J. Biol. Inorg. Chem. 14(5), 643–651 (2009).  https://doi.org/10.1007/s00775-009-0511-yCrossRefGoogle Scholar
  46. 46.
    Trewick, S.C., Henshaw, T.F., Hausinger, R.P., Lindahl, T., Sedgwick, B.: Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage. Nature 419(6903), 174–178 (2002).  https://doi.org/10.1038/nature00908CrossRefGoogle Scholar
  47. 47.
    Vaillancourt, F.H., Barbosa, C.J., Spiro, T.G., Bolin, J.T., Blades, M.W., Turner, R.F.B., Eltis, L.D.: Definitive evidence for monoanionic binding of 2,3- dihydroxybiphenyl to 2,3-dihydroxybiphenyl 1,2-dioxygenase from UV resonance Raman spectroscopy, UV/Vis absorption spectroscopy, and crystallography. J. Am. Chem. Soc. 124(11), 2485–2496 (2002).  https://doi.org/10.1021/ja0174682CrossRefGoogle Scholar
  48. 48.
    Wójcik, A., Broclawik, E., Siegbahn, P.E.M., Lundberg, M., Moran, G., Borowski, T.: Role of Substrate Positioning in the Catalytic Reaction of 4-Hydroxyphenylpyruvate Dioxygenase - A QM/MM Study. J. Am. Chem. Soc. 136(41), 14472–14485 (2014).  https://doi.org/10.1021/ja506378uCrossRefGoogle Scholar
  49. 49.
    Ye, S., Riplinger, C., Hansen, A., Krebs, C., Bollinger, J.M., Neese, F.: Electronic structure analysis of the oxygen-activation mechanism by Fe(II)- and \(\alpha \)-ketoglutarate (\(\alpha \)kg)-dependent dioxygenases. Chemistry 18(21), 6555–6567 (2012).  https://doi.org/10.1002/chem.201102829CrossRefGoogle Scholar
  50. 50.
    Zhou, J., Kelly, W.L., Bachmann, B.O., Gunsior, M., Townsend, C.A., Solomon, E.I.: Spectroscopic studies of substrate interactions with clavaminate synthase 2, a multifunctional \(\alpha \)-KG-dependent non-heme iron enzyme: Correlation with mechanisms and reactivities. J. Am. Chem. Soc. 123, 7388–7398 (2001)CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of SciencesKrakowPoland

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