Computer simulations of quantum tunnelling in enzyme-catalysed hydrogen transfer reactions

Interdisciplinary Sciences, Computational Life Sciences
Kara E Ranaghan, Adrian J Mulholland

Abstract

Transfer of hydrogen as a proton, hydride or hydrogen atom is an important step in many enzymic reactions. Experiments show kinetic isotope effects (KIEs) for some enzyme-catalysed hydrogen transfer reactions that deviate significantly from the limits imposed by considering the differences in mass of the isotopes alone (i.e. the semiclassical limit). These KIEs can be explained if the transfer of the hydrogen species occurs via a quantum mechanical tunnelling mechanism. The unusual temperature dependence of some KIEs has led to suggestions that enzymes have evolved to promote tunnelling through dynamics - a highly controversial hypothesis. Molecular simulations have a vital role in resolving these questions, providing a level of detail of analysis not possible through experiments alone. Here, we review computational molecular modelling studies of quantum tunnelling in enzymes, in particular focusing on the enzymes soybean lipoxygenase-1 (SLO-1), dihydrofolate reductase (DHFR), methylamine dehydrogenase (MADH) and aromatic amine dehydrogenase (AADH) to illustrate the current controversy regarding the importance of quantum effects in enzyme catalysis.

References

Mar 10, 1989·Science·Y ChaJ P Klinman
Oct 28, 1988·Science·J Kraut
Jan 1, 1995·Methods in Enzymology·B J Bahnson, J P Klinman
Nov 14, 1997·Proceedings of the National Academy of Sciences of the United States of America·D Antoniou, S D Schwartz
Mar 13, 1999·Biochemistry·J BasranN S Scrutton
Jun 25, 1999·Chemistry & Biology·A Kohen, J P Klinman
Aug 30, 2001·Journal of the American Chemical Society·P F FaulderN A Burton
Nov 8, 2001·Journal of the American Chemical Society·S R BilleterS Hammes-Schiffer
Dec 19, 2001·Accounts of Chemical Research·R Wolfenden, M J Snider
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Pratul K AgarwalSharon Hammes-Schiffer
Mar 28, 2002·Journal of the American Chemical Society·Stavros CaratzoulasSteven D Schwartz
Apr 11, 2002·Journal of the American Chemical Society·Amnon Kohen, Jan H Jensen
Apr 11, 2002·Journal of the American Chemical Society·Michael J KnappJudith P Klinman
Jun 19, 2002·Accounts of Chemical Research·Donald G TruhlarJordi Villà
Jun 27, 2002·European Journal of Biochemistry·Dimitri AntoniouSteven D Schwartz
Jun 27, 2002·European Journal of Biochemistry·Michael J Knapp, Judith P Klinman
Jul 11, 2002·Journal of the American Chemical Society·Wilson A FranciscoJudith P Klinman
Nov 6, 2002·Biochemistry·Sharon Hammes-Schiffer
Dec 24, 2002·Journal of Computational Chemistry·Mireia Garcia-VilocaJiali Gao
Feb 18, 2003·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Nicolai Lehnert, Edward I Solomon
Apr 24, 2003·Journal of the American Chemical Society·Luis G ArnautMonica Barroso
Aug 30, 2003·Science·Stephen J Benkovic, Sharon Hammes-Schiffer
Sep 4, 2003·Journal of the American Chemical Society·Kenneth M DollRichard G Finke
Oct 30, 2003·Journal of the American Chemical Society·Giovanni Maglia, Rudolf K Allemann
Jan 13, 2004·Science·Mireia Garcia-VilocaDonald G Truhlar
Mar 5, 2004·Journal of the American Chemical Society·Mats H M OlssonArieh Warshel
Apr 15, 2004·Journal of the American Chemical Society·R Steven SikorskiAmnon Kohen

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Citations

Dec 21, 2010·Biochimica Et Biophysica Acta·John D McGeaghAdrian J Mulholland
Mar 3, 2011·Chembiochem : a European Journal of Chemical Biology·André NadlerUlf Diederichsen
Mar 19, 2016·Angewandte Chemie·Jan Meisner, Johannes Kästner
Nov 20, 2016·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Theodros Zelleke, Dominik Marx
Mar 24, 2010·Chemical Communications : Chem Comm·Richard LonsdaleAdrian J Mulholland
Dec 30, 2014·Theoretical Biology & Medical Modelling·Jack A TuszynskiRabab M Abou El-Magd
Feb 23, 2019·Journal of Chemical Information and Modeling·Kara E RanaghanAdrian J Mulholland

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