Theory Uncovers the Role of the Methionine–Tyrosine–Tryptophan Radical Adduct in the Catalase Reaction of KatGs: O2 Release Mediated by Proton-Coupled Electron Transfer
Dr. Binju Wang
Departament de Química Inorgànica i Orgànica, (secció de Química Orgànica) &, Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain
Search for more papers by this authorProf. Dr. Ignacio Fita
Instituto de Biología Molecular (IBMB-CSIC) and, Maria de Maeztu Unit of Excellence. Barcelona Science Park, Baldiri i Reixac 10., 08028 Barcelona, Spain
Search for more papers by this authorCorresponding Author
Prof. Dr. Carme Rovira
Departament de Química Inorgànica i Orgànica, (secció de Química Orgànica) &, Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain
Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, 08010 Barcelona, Spain
Search for more papers by this authorDr. Binju Wang
Departament de Química Inorgànica i Orgànica, (secció de Química Orgànica) &, Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain
Search for more papers by this authorProf. Dr. Ignacio Fita
Instituto de Biología Molecular (IBMB-CSIC) and, Maria de Maeztu Unit of Excellence. Barcelona Science Park, Baldiri i Reixac 10., 08028 Barcelona, Spain
Search for more papers by this authorCorresponding Author
Prof. Dr. Carme Rovira
Departament de Química Inorgànica i Orgànica, (secció de Química Orgànica) &, Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain
Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, 08010 Barcelona, Spain
Search for more papers by this authorGraphical Abstract
QM/MM calculations and QM/MM metadynamics simulations have uncovered the precise catalytic role of the M-Y-W cation radical adduct in the catalase reaction of KatGs. Our results demonstrate that O2 formation proceeds through a mechanism involving proton-coupled electron transfer, which is mediated by the M-Y-W cation radical adduct.
Abstract
Catalase–peroxidases (KatGs) are bifunctional enzymes exhibiting both peroxidase and substantial catalase activities. It is widely recognized from experiments that the catalatic activity of KatGs is correlated with a unique covalent adduct (M-Y-W) formed in the active site, but the exact role of this adduct was elusive up to now. Here, quantum mechanical/molecular mechanical (QM/MM) calculations and QM/MM metadynamics are employed to elucidate the molecular mechanism and the role of M-Y-W adduct in the catalase reaction. It is shown that O2 formation proceeds through a mechanism involving proton-coupled electron transfer (PCET). The M-Y-W cation radical adduct, which is close to the heme, His112 and the HOO. radical intermediate, acts as an electron sink during the PCET process. The present study also highlights the structural differences and functional similarities between KatGs and monofunctional catalases.
Conflict of interest
The authors declare no conflict of interest.
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References
- 1M. Zamocky, P. G. Furtmuller, C. Obinger, Antioxid. Redox Signaling 2008, 10, 1527–1547.
- 2
- 2aA. Claiborne, I. Fridovich, J. Biol. Chem. 1979, 254, 4245–4252;
- 2bA. Díaz, P. C. Loewen, I. Fita, X. Carpena, Arch. Biochem. Biophys. 2012, 525, 102–110;
- 2cI. Fita, X. Carpena, P. C. Loewen in Heme Peroxidases (Eds.: ), Royal Society of Chemistry, Cambridge, UK, 2016, pp. 135–155, ;
- 2dB. Gasselhuber, C. Jakopitsch, M. Zamocky, P. G. Furtmuller, C. Obinger in Heme Peroxidases (Eds.: ), Royal Society of Chemistry, Cambridge, UK, 2016, pp. 156–180.
- 3T. L. Poulos, Chem. Rev. 2014, 114, 3919–3962.
- 4
- 4aJ. Vlasits, C. Jakopitsch, M. Bernroitner, M. Zamocky, P. G. Furtmuller, C. Obinger, Arch. Biochem. Biophys. 2010, 500, 74–81;
- 4bC. Jakopitsch, J. Vlasits, B. Wiseman, P. C. Loewen, C. Obinger, Biochemistry 2007, 46, 1183–1193.
- 5L. J. Donald, O. V. Krokhin, H. W. Duckworth, B. Wiseman, T. Deemagarn, R. Singh, J. Switala, X. Carpena, I. Fita, P. C. Loewen, J. Biol. Chem. 2003, 278, 35687–35692.
- 6C. Jakopitsch, D. Kolarich, G. Petutschnig, P. G. Furtmuller, C. Obinger, FEBS Lett. 2003, 552, 135–140.
- 7
- 7aG. Smulevich, C. Jakopitsch, E. Droghetti, C. Obinger, J. Inorg. Biochem. 2006, 100, 568–585;
- 7bA. Hillar, B. Peters, R. Pauls, A. Loboda, H. Zhang, A. G. Mauk, P. C. Loewen, Biochemistry 2000, 39, 5868–5875;
- 7cX. Zhao, J. Suarez, A. Khajo, S. Yu, L. Metlitsky, R. S. Magliozzo, J. Am. Chem. Soc. 2010, 132, 8268–8269;
- 7dR. A. Ghiladi, G. M. Knudsen, K. F. Medzihradszky, P. R. Ortiz de Montellano, J. Biol. Chem. 2005, 280, 22651–22663;
- 7eC. Jakopitsch, A. Ivancich, F. Schmuckenschlager, A. Wanasinghe, G. Pöltl, P. G. Furtmüller, F. Rüker, C. Obinger, J. Biol. Chem. 2004, 279, 46082–46095.
- 8
- 8aP. Vidossich, M. Alfonso-Prieto, X. Carpena, P. C. Loewen, I. Fita, C. Rovira, J. Am. Chem. Soc. 2007, 129, 13436–13446;
- 8bP. Vidossich, X. Carpena, P. C. Loewen, I. Fita, C. Rovira, J. Phys. Chem. Lett. 2011, 2, 196–200;
- 8cP. C. Loewen, X. Carpena, P. Vidossich, I. Fita, C. Rovira, J. Am. Chem. Soc. 2014, 136, 7249–7252;
- 8dB. I. Kruft, R. S. Magliozzo, A. A. Jarzecki, J. Phys. Chem. A 2015, 119, 6850–6866.
- 9X. Carpena, B. Wiseman, T. Deemagarn, R. Singh, J. Switala, A. Ivancich, I. Fita, P. C. Loewen, EMBO Rep. 2005, 6, 1156–1162.
- 10T. L. Poulos, J. Kraut, J. Biol. Chem. 1980, 255, 8199–8205.
- 11
- 11aE. Derat, S. Shaik, C. Rovira, P. Vidossich, M. Alfonso-Prieto, J. Am. Chem. Soc. 2007, 129, 6346–6347;
- 11bP. Vidossich, G. Fiorin, M. Alfonso-Prieto, E. Derat, S. Shaik, C. Rovira, J. Phys. Chem. B 2010, 114, 5161–5169.
- 12
- 12aA. Warshel, Angew. Chem. Int. Ed. 2014, 53, 10020–10031;
Angew. Chem. 2014, 126, 10182–10194;
10.1002/ange.201403689 Google Scholar
- 12bH. M. Senn, W. Thiel, Angew. Chem. Int. Ed. 2009, 48, 1198–1229;
Angew. Chem. 2009, 121, 1220–1254;
10.1002/ange.200802019 Google Scholar
- 12cH. Lin, D. G. Truhlar, Theor. Chem. Acc. 2007, 117, 185–199;
- 12dM. W. van der Kamp, A. J. Mulholland, Biochemistry 2013, 52, 2708–2728.
- 13
- 13aD. Kumar, W. Thiel, S. P. de Visser, J. Am. Chem. Soc. 2011, 133, 3869–3882;
- 13bP. Schyman, W. Z. Lai, H. Chen, Y. Wang, S. Shaik, J. Am. Chem. Soc. 2011, 133, 7977–7984;
- 13cB. Wang, D. Usharani, C. Li, S. Shaik, J. Am. Chem. Soc. 2014, 136, 13895–13901;
- 13dB. Wang, C. Li, K. D. Dubey, S. Shaik, J. Am. Chem. Soc. 2015, 137, 7379–7390;
- 13eA. Li, B. Wang, A. Ilie, K. D. Dubey, G. Bange, I. V. Korendovych, S. Shaik, M. T. Reetz, Nat. Commun. 2017, 8, 14876.
- 14
- 14aA. Laio, M. Parrinello, Proc. Natl. Acad. Sci. USA 2002, 99, 12562–12566;
- 14bA. Barducci, G. Bussi, M. Parrinello, Phys. Rev. Lett. 2008, 100, 1–4.
- 15M. Alfonso-Prieto, X. Biarnes, P. Vidossich, C. Rovira, J. Am. Chem. Soc. 2009, 131, 11751–11761.
- 16
- 16aY. Yamada, T. Fujiwara, T. Sato, N. Igarashi, N. Tanaka, Nat. Struct. Biol. 2002, 9, 691–695; Accession PDB Code: 1ITK;
- 16bT. Bertrand, N. A. J. Eady, J. N. Jones, J. M. Nagy, B. Jamart-Grégoire, E. L. Raven, K. A. Brown, J. Biol. Chem. 2004, 279, 38991–38999; Accession PDB code: 1SJ2.
- 17P. Campomanes, U. Roethlisberger, M. Alfonso-Prieto, C. Rovira, J. Am. Chem. Soc. 2015, 137, 11170–11178.
- 18M. Machuqueiro, B. L. Victor, J. Switala, J. Villanueva, C. Rovira, I. Fita, P. C. Loewen, Biochemistry 2017, 56, 2271–2281.
- 19
- 19aO. J. Njuma, I. Davis, E. N. Ndontsa, J. R. Krewall, A. Liu, D. C. Goodwin, J. Biol. Chem. 2017, 292, 18408–18421;
- 19bX. Zhao, A. Khajo, S. Jarrett, J. Suarez, Y. Levitsky, R. M. Burger, A. A. Jarzecki, R. S. Magliozzo, J. Biol. Chem. 2012, 287, 37057–37065;
- 19cB. Gasselhuber, M. M. Graf, C. Jakopitsch, M. Zamocky, A. Nicolussi, P. G. Furtmuller, C. Oostenbrink, X. Carpena, C. Obinger, Biochemistry 2016, 55, 3528–3541.
- 20M. H. Olsson, C. R. Søndergard, M. Rostkowski, J. H. Jensen, J. Chem. Theory Comput. 2011, 7, 525–537.
- 21
- 21aP. Li, K. M. Merz Jr., J. Chem. Inf. Model. 2016, 56, 599–604;
- 21bP. Li, K. M. Merz Jr., Chem. Rev. 2017, 117, 1564–1686.
- 22J. A. Maier, C. Martinez, K. Kasavajhala, L. Wickstrom, K. E. Hauser, C. Simmerling, J. Chem. Theory Comput. 2015, 11, 3696–3713.
- 23J. A. Izaguirre, D. P. Catarello, J. M. Wozniak, R. D. Skeel, J. Chem. Phys. 2001, 114, 2090–2098.
- 24H. J. C. Berendsen, J. P. M. Postma, W. F. van Gunsteren, A. DiNola, J. R. Haak, J. Chem. Phys. 1984, 81, 3684–3690.
- 25T. Darden, D. York, L. Pedersen, J. Chem. Phys. 1993, 98, 10089–10092.
- 26AMBER 2017, D. A. Case, D. S. Cerutti, T. E. Cheatham III, T. A. Darden, R. E. Duke, T. J. Giese, H. Gohlke, A. W. Goetz, D. Greene, N. Homeyer, S. Izadi, A. Kovalenko, T. S. Lee, S. LeGrand, P. Li, C. Lin, J. Liu, T. Luchko, R. Luo, D. Mermelstein, K. M. Merz, G. Monard, H. Nguyen, I. Omelyan, A. Onufriev, F. Pan, R. Qi, D. R. Roe, A. Roitberg, C. Sagui, C. L. Simmerling, W. M. Botello-Smith, J. Swails, R. C. Walker, J. Wang, R. M. Wolf, X. Wu, L. Xiao, D. M. York, P. A. Kollman, 2017, University of California, San Francisco.
- 27
- 27aP. Sherwood, A. H. de Vries, M. F. Guest, G. Schreckenbach, C. R. A. Catlow, S. A. French, A. A. Sokol, S. T. Bromley, W. Thiel, A. J. Turner, S. Billeter, F. Terstegen, S. Thiel, J. Kendrick, S. C. Rogers, J. Casci, M. Watson, F. King, E. Karlsen, M. Sjovoll, A. Fahmi, A. Schäfer, C. J. Lennartz, J. Mol. Struct. 2003, 632, 1–28;
- 27bS. Metz, J. Kästner, A. Sokol, T. Keal, P. Sherwood, WIREs Comput. Mol. Sci. 2014, 4, 101–110.
- 28R. Ahlrichs, M. Bär, M. Häser, H. Horn, C. Kölmel, Chem. Phys. Lett. 1989, 162, 165–169.
- 29W. Smith, T. R. Forester, J. Mol. Graphics 1996, 14, 136–141.
- 30B. R. Brooks, C. L. Brooks III, A. D. MacKerell Jr, L. Nilsson, R. J. Petrella, B. Roux, Y. Won, G. Archontis, C. Bartels, S. Boresch, A. Caflisch, L. Caves, Q. Cui, A. R. Dinner, M. Feig, S. Fischer, J. Gao, M. Hodoscek, W. Im, K. Kuczera, T. Lazaridis, J. Ma, V. Ovchinnikov, E. Paci, R. W. Pastor, C. B. Post, J. Z. Pu, M. Schaefer, B. Tidor, R. M. Venable, H. L. Woodcock, X. Wu, W. Yang, D. M. York, M. Karplus, J. Comput. Chem. 2009, 30, 1545–1614.
- 31D. Bakowies, W. Thiel, J. Phys. Chem. 1996, 100, 10580–10594.
- 32A. D. Becke, J. Chem. Phys. 1993, 98, 5648–5652.
- 33S. R. Billeter, A. J. Turner, W. Thiel, Phys. Chem. Chem. Phys. 2000, 2, 2177–2186.
- 34S. Grimme, J. Antony, S. Ehrlich, H. Krieg, J. Chem. Phys. 2010, 132, 154104-154109.
- 35
- 35aCP2K version 4.1, the CP2K developers group, 2016. CP2K is freely available from http://https://www.cp2k.org/;
- 35bJ. VandeVondele, Comput. Phys. Commun. 2005, 167, 103–128.
- 36
- 36aT. Laino, F. Mohamed, A. Laio, M. Parrinello, J. Chem. Theory Comput. 2005, 1, 1176–1184;
- 36bA. Laio, J. VandeVondele, U. Rothlisberger, J. Chem. Phys. 2002, 116, 6941–6947.
- 37J. VandeVondele, J. Hutter, J. Chem. Phys. 2007, 127, 114105.
- 38
- 38aS. Goedecker, M. Teter, J. Hutter, Phys. Rev. B: Condens. Matter Mater. Phys. 1996, 54, 1703–1710;
- 38bC. Hartwigsen, S. Goedecker, J. Hutter, Phys. Rev. B: Condens. Matter Mater. Phys. 1998, 58, 3641–3662.
- 39M. Guidon, J. Hutter, J. VandeVondele, J. Chem. Theory Comput. 2010, 6, 2348–2364.
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