Skip to main content
SpringerLink
Log in

Bioinorganic Reaction Mechanisms—Quantum Chemistry Approach

  • Chapter
  • First Online:
Computational Methods to Study the Structure and Dynamics of Biomolecules and Biomolecular Processes

Part of the book series: Springer Series on Bio- and Neurosystems ((SSBN,volume 8))

  • 788 Accesses

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Antosiewicz, J., Shugar, D.: Poisson–Boltzmann continuum-solvation models: applications to pH-dependent properties of biomolecules. Mol. Biosyst. 7, 2923–2949 (2011)

    Article  Google Scholar 

  2. Becke, A.D.J.: Density-functional thermochemistry. III. The role of exact exchange. Chem. Phys. 98, 5648–5652 (1993)

    Google Scholar 

  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/jp010305f

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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.200305306

    Article  Google Scholar 

  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/s00894-010-0652-5

    Article  Google Scholar 

  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/ja101877a

    Article  Google Scholar 

  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/s00775-012-0904-1

    Article  Google Scholar 

  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/bi701438r

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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/10.1038/44400

    Article  Google Scholar 

  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.202614999

    Article  Google Scholar 

  13. Dellago, C., Bolhuis, P.G.: Transition path sampling simulations of biological systems. Top. Curr. Chem. 268, 291–317 (2007)

    Article  Google Scholar 

  14. Evans, D.A., Wales, D.J.: Free energy landscapes of model peptides and proteins. J. Chem. Phys. 118, 3891 (2003)

    Article  Google Scholar 

  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/nchembio0207-86

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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.21458

    Article  Google Scholar 

  18. Grimme, S.: Semiempirical GGA-type density functional constructed with a long-range dispersion correction. J. Comput. Chem. 27, 1787–1799 (2006)

    Article  Google Scholar 

  19. Hammes-Schiffer, S.: Theory of proton-coupled electron transfer in energy conversion processes. Acc. Chem. Res. 42, 1881–1889 (2009)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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/10.1080/10409230490440541

    Article  Google Scholar 

  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/nature03924

    Article  Google Scholar 

  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/cr9500390

    Article  Google Scholar 

  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. 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)

    Article  Google Scholar 

  27. Kovaleva, E.G., Lipscomb, J.D.: Intermediate in the O–O bond cleavage reaction of an extradiol dioxygenase. Biochemistry 47, 11168–11170 (2008)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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. 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/bi048518t

    Article  Google Scholar 

  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.201202825

    Article  Google Scholar 

  33. Moran, G.R.: 4-Hydroxyphenylpyruvate dioxygenase. Arch. Biochem. Biophys. 433(1), 117–128 (2005). https://doi.org/10.1016/j.abb.2004.08.015

    Article  Google Scholar 

  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/nature05971

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  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/ar300067g

    Article  Google Scholar 

  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)

    Article  Google Scholar 

  39. Senn, H., Thiel, W.: QM/MM methods for biological systems. Top. Curr. Chem. 268, 173–290 (2007)

    Article  Google Scholar 

  40. Sheppard, D., Terrell, R., Henkelman, G.: Optimization methods for finding minimum energy paths. J. Chem. Phys. 128(134), 106 (2008)

    Google Scholar 

  41. Siegbahn, P.E.M.: Modeling aspects of mechanisms for reactions catalyzed by metalloenzymes. J. Comput. Chem. 22, 1634–1645 (2001)

    Article  Google Scholar 

  42. Siegbahn, P.E.M.: Mechanisms of metalloenzymes studied by quantum chemical methods. Q. Rev. Biophys. 36, 91–145 (2003)

    Article  Google Scholar 

  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/ar050123u

    Article  Google Scholar 

  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/ja0493805

    Article  Google Scholar 

  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-y

    Article  Google Scholar 

  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/nature00908

    Article  Google Scholar 

  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/ja0174682

    Article  Google Scholar 

  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/ja506378u

    Article  Google Scholar 

  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.201102829

    Article  Google Scholar 

  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)

    Article  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, ul. Niezapominajek 8, 30-239, Krakow, Poland

    Tomasz Borowski & Ewa Broclawik

Authors
  1. Tomasz Borowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ewa Broclawik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Tomasz Borowski or Ewa Broclawik .

Editor information

Editors and Affiliations

  1. Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland

    Adam Liwo

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Borowski, T., Broclawik, E. (2019). Bioinorganic Reaction Mechanisms—Quantum Chemistry Approach. In: Liwo, A. (eds) Computational Methods to Study the Structure and Dynamics of Biomolecules and Biomolecular Processes. Springer Series on Bio- and Neurosystems, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-319-95843-9_24

Download citation

Publish with us

Policies and ethics

Search

Navigation