Abstract
Over the last 10 years, studies of enzyme systems have demonstrated that, in many cases, H-transfers occur by a quantum mechanical tunneling mechanism analogous to long-range electron transfer. H-transfer reactions can be described by an extension of Marcus theory and, by substituting hydrogen with deuterium (or even tritium), it is possible to explore this theory in new ways by employing kinetic isotope effects. Because hydrogen has a relatively short deBroglie wavelength, H-transfers are controlled by the width of the reaction barrier. By coupling protein dynamics to the reaction coordinate, enzymes have the potential ability to facilitate more efficient H-tunneling by modulating barrier properties. In this review, we describe recent advances in both experimental and theoretical studies of enzymatic H-transfer, in particular the role of protein dynamics or promoting motions. We then discuss possible consequences with regard to tyrosine oxidation/reduction kinetics in Photosystem II.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Notes
H-transfer reactions are defined here as those reactions involving either H (protium), D (deuterium), or T (tritium), and where the transfer of either a proton, hydrogen atom (H·), or hydride (H−) occurs.
\( \Updelta E_{{\text{a}}} = E_{{\text{a}}} ^{D} - E_{{\text{a}}} ^{H} \) where E a is the activation energy (or enthalpy) of the reaction. ΔE a is equivalent to \( \Updelta \Updelta H^{\ddag } \).
Abbreviations
- D:
-
Deuterium
- DHFR:
-
Dihydrofolate reductase
- ECHT:
-
Environmentally coupled H-transfer
- ET:
-
Electron transfer
- H:
-
Hydrogen or protium
- KIE:
-
Kinetic isotope effect
- PS II:
-
Photosystem II
- QMT:
-
Quantum mechanical tunneling
- T:
-
Tritium
- TST:
-
Transition state theory
- ZPE:
-
Zero point energy
References
Allemann RK, Evans RM, Tey LH, Maglia G, Pang JY, Rodriguez R et al (2006) Protein motions during catalysis by dihydrofolate reductases. Philos Trans R Soc Lond B Biol Sci 361:1317–1321. doi:10.1098/rstb.2006.1865
Antoniou D, Schwartz SD (1997) Large kinetic isotope effects in enzymatic proton transfer and the role of substrate oscillations. Proc Natl Acad Sci USA 94:12360–12365. doi:10.1073/pnas.94.23.12360
Ball P (2004) Enzymes—by chance, or by design? Nature 431:396–397. doi:10.1038/431396a
Basran J, Sutcliffe MJ, Scrutton NS (1999) Enzymatic H-transfer requires vibration-driven extreme tunneling. Biochemistry 38:3218–3222. doi:10.1021/bi982719d
Basran J, Harris RJ, Sutcliffe MJ, Scrutton NS (2003) H-tunneling in the multiple H-transfers of the catalytic cycle of morphinone reductase and in the reductive half-reaction of the homologous pentaerythritol tetranitrate reductase. J Biol Chem 278:43973–43982. doi:10.1074/jbc.M305983200
Bell R (1980) The tunnel effect in chemistry. Chapman and Hall, London
Benkovic SJ, Hammes-Schiffer S (2003) A perspective on enzyme catalysis. Science 301:1196–1202. doi:10.1126/science.1085515
Benkovic SJ, Hammes-Schiffer S (2006) Biochemistry—enzyme motions inside and out. Science 312:208–209. doi:10.1126/science.1127654
Boehr DD, McElheny D, Dyson HJ, Wright PE (2006) The dynamic energy landscape of dihydrofolate reductase catalysis. Science 313:1638–1642. doi:10.1126/science.1130258
Borgis D, Hynes JT (1996) Curve crossing formulation for proton transfer reactions in solution. J Phys Chem 100:1118–1128. doi:10.1021/jp9522324
Bruno WJ, Bialek W (1992) Vibrationally enhanced tunneling as a mechanism for enzymatic hydrogen transfer. Biophys J 63:689–699
Caratzoulas S, Mincer JS, Schwartz SD (2002) Identification of a protein-promoting vibration in the reaction catalyzed by horse liver alcohol dehydrogenase. J Am Chem Soc 124:3270–3276. doi:10.1021/ja017146y
Cha Y, Murray CJ, Klinman JP (1989) Hydrogen tunneling in enzyme-reactions. Science 243:1325–1330. doi:10.1126/science.2646716
Cleland WW (2003) The use of isotope effects to determine enzyme mechanisms. J Biol Chem 278:51975–51984. doi:10.1074/jbc.X300005200
Cukier RI, Nocera DG (1998) Proton-coupled electron transfer. Annu Rev Phys Chem 49:337–369. doi:10.1146/annurev.physchem.49.1.337
Faller P, Goussias C, Rutherford AW, Un S (2003) Resolving intermediates in biological proton-coupled electron transfer: a tyrosyl radical prior to proton movement. Proc Natl Acad Sci USA 100:8732–8735. doi:10.1073/pnas.1530926100
Ferreira KN, Iverson TM, Maghlaoui K, Barber J, Iwata S (2004) Architecture of the photosynthetic oxygen-evolving center. Science 303:1831–1838. doi:10.1126/science.1093087
Garcia-Viloca M, Truhlar DG, Gao JL (2003) Reaction-path energetics and kinetics of the hydride transfer reaction catalyzed by dihydrofolate reductase. Biochemistry 42:13558–13575. doi:10.1021/bi034824f
Garcia-Viloca M, Gao J, Karplus M, Truhlar DG (2004) How enzymes work: analysis by modern rate theory and computer simulations. Science 303:186–195. doi:10.1126/science.1088172
Gladstone S, Laidler KJ, Eyring H (1951) The theory of rate processes. McGraw-Hill, New York
Grant KL, Klinman JP (1989) Evidence that both protium and deuterium undergo significant tunneling in the reaction catalyzed by bovine serum amine oxidase. Biochemistry 28:6597–6605. doi:10.1021/bi00442a010
Hammes-Schiffer S (2006) Hydrogen tunneling and protein motion in enzyme reactions. Acc Chem Res 39:93–100. doi:10.1021/ar040199a
Hammes-Schiffer S, Watney JB (2006) Hydride transfer catalysed by Escherichia coli and Bacillus subtilis dihydrofolate reductase: coupled motions and distal mutations. Philos Trans R Soc Lond B Biol Sci 361:1365–1373. doi:10.1098/rstb.2006.1869
Hammes-Schiffer S, Hatcher E, Ishikita H, Skone JH, Soudackov AV (2008) Theoretical studies of proton-coupled electron transfer: models and concepts relevant to bioenergetics. Coord Chem Rev 252:384–394. doi:10.1016/j.ccr.2007.07.019
Harris RJ, Meskys R, Sutcliffe MJ, Scrutton NS (2000) Kinetic studies of the mechanism of carbon-hydrogen bond breakage by the heterotetrameric sarcosine oxidase of Arthrobacter sp 1-IN. Biochemistry 39:1189–1198. doi:10.1021/bi991941v
Hay S, Westerlund K, Tommos C (2005) Moving a phenol hydroxyl group from the surface to the interior of a protein: effects on the phenol potential and pK(A). Biochemistry 44:11891–11902. doi:10.1021/bi050901q
Hay S, Sutcliffe MJ, Scrutton NS (2007) Promoting motions in enzyme catalysis probed by pressure studies of kinetic isotope effects. Proc Natl Acad Sci USA 104:507–512. doi:10.1073/pnas.0608408104
Hay S, Pudney C, Hothi P, Johannissen LO, Masgrau L, Pang J et al (2008a) Atomistic insight into the origin of the temperature-dependence of kinetic isotope effects and H-tunnelling in enzyme systems is revealed through combined experimental studies and biomolecular simulation. Biochem Soc Trans 36:16–21. doi:10.1042/BST0360016
Hay S, Pudney CR, Sutcliffe MJ, Scrutton NS (2008b) Are environmentally coupled enzymatic hydrogen tunneling reactions influenced by changes in solution viscosity? Angew Chem Int Ed 47:537–540. doi:10.1002/anie.200704484
Hay S, Sutcliffe MJ, Scrutton NS (2008c) Probing coupled motions in enzymatic hydrogen tunnelling reactions: beyond temperature-dependence studies of kinetic isotope effects. In: Allemann RK, Scrutton NS (eds) Quantum tunnelling in enzyme catalyzed reactions. Royal Society of Chemistry (in press)
Hodgkiss JM, Damrauer NH, Presse S, Rosenthal J, Nocera DG (2006) Electron transfer driven by proton fluctuations in a hydrogen-bonded donor-acceptor assembly. J Phys Chem B 110:18853–18858. doi:10.1021/jp056703q
Hoganson CW, LydakisSimantiris N, Tang XS, Tommos C, Warncke K, Babcock GT, Diner BA, McCracken J, Styring S (1995) A hydrogen-atom abstraction model for the function of Y-Z in photosynthetic oxygen evolution. Photosynth Res 46:177–184. doi:10.1007/BF00020428
Johannissen LO, Hay S, Scrutton NS, Sutcliffe MJ (2007) Proton tunneling in aromatic amine dehydrogenase is driven by a short-range sub-picosecond promoting vibration: consistency of simulation and theory with experiment. J Phys Chem B 111:2631–2638. doi:10.1021/jp066276w
Jonsson T, Edmondson DE, Klinman JP (1994) Hydrogen tunneling in the flavoenzyme monoamine-oxidase-B. Biochemistry 33:14871–14878. doi:10.1021/bi00253a026
Karge M, Irrgang KD, Sellin S, Feinaugle R, Liu B, Eckert HJ et al (1996) Effects of hydrogen deuterium exchange on photosynthetic water cleavage in PS II core complexes from spinach. FEBS Lett 378:140–144. doi:10.1016/0014-5793(95)01433-0
Karge M, Irrgang KD, Renger G (1997) Analysis of the reaction coordinate of photosynthetic water oxidation by kinetic measurements of 355 nm absorption changes at different temperatures in Photosystem II preparations suspended in either H2O or D2O. Biochemistry 36:8904–8913. doi:10.1021/bi962342g
Klinman JP (2006) The role of tunneling in enzyme catalysis of C–H activation. Biochim Biophys Acta 1757:981–987. doi:10.1016/j.bbabio.2005.12.004
Knapp MJ, Klinman JP (2002) Environmentally coupled hydrogen tunneling—linking catalysis to dynamics. Eur J Biochem 269:3113–3121. doi:10.1046/j.1432-1033.2002.03022.x
Knapp MJ, Rickert K, Klinman JP (2002) Temperature-dependent isotope effects in soybean lipoxygenase-1: correlating hydrogen tunneling with protein dynamics. J Am Chem Soc 124:3865–3874. doi:10.1021/ja012205t
Kohen A, Klinman JP (1999) Hydrogen tunneling in biology. Chem Biol 6:R191–R198. doi:10.1016/S1074-5521(99)80058-1
Kohen A, Jonsson T, Klinman JP (1997) Effects of protein glycosylation on catalysis: changes in hydrogen tunneling and enthalpy of activation in the glucose oxidase reaction. Biochemistry 36:6854–6854. doi:10.1021/bi975003b
Kohen A, Cannio R, Bartolucci S, Klinman JP (1999) Enzyme dynamics and hydrogen tunnelling in a thermophilic alcohol dehydrogenase. Nature 399:496–499. doi:10.1038/20981
Kuznetsov AM, Ulstrup J (1999) Proton and hydrogen atom tunnelling in hydrolytic and redox enzyme catalysis. Can J Chem 77:1085–1096. doi:10.1139/cjc-77-5-6-1085
Loll B, Kern J, Saenger W, Zouni A, Biesiadka J (2005) Towards complete cofactor arrangement in the 3.0 angstrom resolution structure of Photosystem II. Nature 438:1040–1044. doi:10.1038/nature04224
Maglia G, Allemann RK (2003) Evidence for environmentally coupled hydrogen tunneling during dihydrofolate reductase catalysis. J Am Chem Soc 125:13372–13373. doi:10.1021/ja035692g
Marcus RA (1956) Theory of oxidation-reduction reactions involving electron transfer. 1. J Chem Phys 24:966–978. doi:10.1063/1.1742723
Marcus RA, Sutin N (1985) Electron transfers in chemistry and biology. Biochim Biophys Acta 811:265–322
Masgrau L, Roujeinikova A, Johannissen LO, Hothi P, Basran J, Ranaghan KE et al (2006) Atomic description of an enzyme reaction dominated by proton tunneling. Science 312:237–241. doi:10.1126/science.1126002
Meyer MP, Tomchick DR, Klinman JP (2008) Enzyme structure and dynamics affect hydrogen tunneling: the impact of a remote side chain (I553) in soybean lipoxygenase–1. Proc Natl Acad Sci USA 105:1146–1151. doi:10.1073/pnas.0710643105
Moser CC, Keske JM, Warncke K, Farid RS, Dutton PL (1992) Nature of biological electron-transfer. Nature 355:796–802. doi:10.1038/355796a0
Pang J, Pu JZ, Gao JL, Truhlar DG, Allemann RK (2006) Hydride transfer reaction catalyzed by hyperthermophilic dihydrofolate reductase is dominated by quantum mechanical tunneling and is promoted by both inter- and intramonomeric correlated motions. J Am Chem Soc 128:8015–8023. doi:10.1021/ja061585l
Pang J, Hay S, Scrutton NS, Sutcliffe MJ (2008) Deep tunneling dominates the biologically important hydride transfer reaction from NADH to FMN in morphinone reductase. J Am Chem Soc 130:7092–7097. doi:10.1021/ja800471f
Petrie S, Stranger R, Gatt P, Pace RJ (2007) Bridge over troubled water: resolving the competing Photosystem II crystal structures. Chemistry—A Eur J 13:5082–5089. doi:10.1002/chem.200700003
Pudney CR, Hay S, Sutcliffe MJ, Scrutton NS (2006) alpha-Secondary isotope effects as probes of “tunneling-ready” configurations in enzymatic H-tunneling: Insight from environmentally coupled tunneling models. J Am Chem Soc 128:14053–14058. doi:10.1021/ja0614619
Pudney CR, Hay S, Pang JY, Costello C, Leys D, Sutcliffe MJ et al (2007) Mutagenesis of morphinone reductase induces multiple reactive configurations and identifies potential ambiguity in kinetic analysis of enzyme tunneling mechanisms. J Am Chem Soc 129:13949–13956. doi:10.1021/ja074463h
Renger G (2007) Oxidative photosynthetic water splitting: energetics, kinetics and mechanism. Photosynth Res 92:407–425. doi:10.1007/s11120-007-9185-x
Rhile IJ, Markle TF, Nagao H, DiPasquale AG, Lam OP, Lockwood MA et al (2006) Concerted proton-electron transfer in the oxidation of hydrogen-bonded phenols. J Am Chem Soc 128:6075–6088. doi:10.1021/ja054167+
Sikorski RS, Wang L, Markham KA, Rajagopalan PTR, Benkovic SJ, Kohen A (2004) Tunneling and coupled motion in the Escherichia coli dihydrofolate reductase catalysis. J Am Chem Soc 126:4778–4779. doi:10.1021/ja031683w
Sjodin M, Styring S, Akermark B, Sun LC, Hammarstrom L (2000) Proton-coupled electron transfer from tyrosine in a tyrosine-ruthenium-tris-bipyridine complex: comparison with tyrosine(z) oxidation in Photosystem II. J Am Chem Soc 122:3932–3936. doi:10.1021/ja993044k
Sjodin M, Irebo T, Utas JE, Lind J, Merenyi G, Akermark B et al (2006) Kinetic effects of hydrogen bonds on proton-coupled electron transfer from phenols. J Am Chem Soc 128:13076–13083. doi:10.1021/ja063264f
Soudackov A, Hammes-Schiffer S (2000) Derivation of rate expressions for nonadiabatic proton-coupled electron transfer reactions in solution. J Chem Phys 113:2385–2396. doi:10.1063/1.482053
Sutcliffe MJ, Masgrau L, Roujeinikova A, Johannissen LO, Hothi P, Basran J et al (2006) Hydrogen tunnelling in enzyme-catalysed H-transfer reactions: flavoprotein and quinoprotein systems. Philos Trans R Soc Lond B Biol Sci 361:1375–1386. doi:10.1098/rstb.2006.1878
Swain CG, Stivers EC, Reuwer JF, Schaad LJ (1958) Use of hydrogen isotope effects to identify the attacking nucleophile in the enolization of ketones catalyzed by acetic acid. J Am Chem Soc 80:5885–5893. doi:10.1021/ja01554a077
Swanwick RS, Maglia G, Tey L, Allemann RK (2006) Coupling of protein motions and hydrogen transfer during catalysis by Escherichia coli dihydrofolate reductase. Biochem J 394:259–265. doi:10.1042/BJ20051464
Tejero I, Garcia-Viloca M, Gonzalez-Lafont A, Lluch JM, York DM (2006) Enzyme dynamics and tunneling enhanced by compression in the hydrogen abstraction catalyzed by soybean lipoxygenase-1. J Phys Chem B 110:24708–24719. doi:10.1021/jp066263i
Tommos C, Babcock GT (2000) Proton and hydrogen currents in photosynthetic water oxidation. Biochim Biophys Acta 1458:199–219. doi:10.1016/S0005-2728(00)00069-4
Tommos C, Skalicky JJ, Pilloud DL, Wand AJ, Dutton PL (1999) De novo proteins as models of radical enzymes. Biochemistry 38:9495–9507. doi:10.1021/bi990609g
Wang L, Goodey NM, Benkovic SJ, Kohen A (2006a) Coordinated effects of distal mutations on environmentally coupled tunneling in dihydrofolate reductase. Proc Natl Acad Sci USA 103:15753–15758. doi:10.1073/pnas.0606976103
Wang L, Goodey NM, Benkovic SJ, Kohen A (2006b) The role of enzyme dynamics and tunnelling in catalysing hydride transfer: studies of distal mutants of dihydrofolate reductase. Philos Trans R Soc Lond B Biol Sci 361:1307–1315. doi:10.1098/rstb.2006.1871
Warshel A, Sharma PK, Kato M, Xiang Y, Liu HB, Olsson MHM (2006) Electrostatic basis for enzyme catalysis. Chem Rev 106:3210–3235. doi:10.1021/cr0503106
Zhang CX (2006) Interaction between tyrosine(Z) and substrate water in active Photosystem II. Biochim Biophys Acta 1757:781–786. doi:10.1016/j.bbabio.2006.05.036
Acknowledgments
SH would like to dedicate this article to Tom Wydrzynski. Funding for work on enzymatic H-transfer was provided by the UK Biotechnology and Biological Sciences Research Council (BBSRC) to N.S.S. N.S.S. is a BBSRC Professorial Research Fellow.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hay, S., Scrutton, N.S. H-transfers in Photosystem II: what can we learn from recent lessons in the enzyme community?. Photosynth Res 98, 169–177 (2008). https://doi.org/10.1007/s11120-008-9326-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11120-008-9326-x