Mechanistic Insight into Peptidyl-Cysteine Oxidation by the Copper-Dependent Formylglycine-Generating Enzyme
Yao Wu
Key Laboratory of Advanced Light Conversion Materials and Biophotonics, Department of Chemistry, Renmin University of China, Beijing, 100872 China
Search for more papers by this authorCong Zhao
Key Laboratory of Advanced Light Conversion Materials and Biophotonics, Department of Chemistry, Renmin University of China, Beijing, 100872 China
Search for more papers by this authorYanzhuang Su
Key Laboratory of Advanced Light Conversion Materials and Biophotonics, Department of Chemistry, Renmin University of China, Beijing, 100872 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Sason Shaik
Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, 91904 Israel
Search for more papers by this authorCorresponding Author
Prof. Dr. Wenzhen Lai
Key Laboratory of Advanced Light Conversion Materials and Biophotonics, Department of Chemistry, Renmin University of China, Beijing, 100872 China
Search for more papers by this authorYao Wu
Key Laboratory of Advanced Light Conversion Materials and Biophotonics, Department of Chemistry, Renmin University of China, Beijing, 100872 China
Search for more papers by this authorCong Zhao
Key Laboratory of Advanced Light Conversion Materials and Biophotonics, Department of Chemistry, Renmin University of China, Beijing, 100872 China
Search for more papers by this authorYanzhuang Su
Key Laboratory of Advanced Light Conversion Materials and Biophotonics, Department of Chemistry, Renmin University of China, Beijing, 100872 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Sason Shaik
Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, 91904 Israel
Search for more papers by this authorCorresponding Author
Prof. Dr. Wenzhen Lai
Key Laboratory of Advanced Light Conversion Materials and Biophotonics, Department of Chemistry, Renmin University of China, Beijing, 100872 China
Search for more papers by this authorAbstract
The copper-dependent formylglycine-generating enzyme (FGE) catalyzes the oxygen-dependent oxidation of specific peptidyl-cysteine residues to formylglycine. Our QM/MM calculations provide a very likely mechanism for this transformation. The reaction starts with dioxygen binding to the tris-thiolate CuI center to form a triplet CuII-superoxide complex. The rate-determining hydrogen atom abstraction involves a triplet-singlet crossing to form a CuII−OOH species that couples with the substrate radical, leading to a CuI-alkylperoxo intermediate. This is accompanied by proton transfer from the hydroperoxide to the S atom of the substrate via a nearby water molecule. The subsequent O−O bond cleavage is coupled with the C−S bond breaking that generates the formylglycine and a CuII-oxyl complex. Moreover, our results suggest that the aldehyde oxygen of the final product originates from O2, which will be useful for future experimental work.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the Supporting Information of this article.
Supporting Information
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
| Filename | Description |
|---|---|
| ange202212053-sup-0001-misc_information.pdf1.6 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1
- 1aR. A. Festa, D. J. Thiele, Curr. Biol. 2011, 21, R877–R883;
- 1bE. I. Solomon, D. E. Heppner, E. M. Johnston, J. W. Ginsbach, J. Cirera, M. Qayyum, M. T. Kieber-Emmons, C. H. Kjaergaard, R. G. Hadt, L. Tian, Chem. Rev. 2014, 114, 3659–3853.
- 2
- 2aE. A. Lewis, W. B. Tolman, Chem. Rev. 2004, 104, 1047–1076;
- 2bA. Bhagi-Damodaran, M. A. Michael, Q. H. Zhu, J. Reed, B. A. Sandoval, E. N. Mirts, S. Chakraborty, P. Moenne-Loccoz, Y. Zhang, Y. Lu, Nat. Chem. 2017, 9, 257–263;
- 2cC. E. Elwell, N. L. Gagnon, B. D. Neisen, D. Dhar, A. D. Spaeth, G. M. Yee, W. B. Tolman, Chem. Rev. 2017, 117, 2059–2107;
- 2dW. Keown, J. B. Gary, T. D. P. Stack, J. Biol. Inorg. Chem. 2017, 22, 289–305;
- 2eM. Wikström, K. Krab, V. Sharma, Chem. Rev. 2018, 118, 2469–2490;
- 2fK. K. Meier, S. M. Jones, T. Kaper, H. Hansson, M. J. Koetsier, S. Karkehabadi, E. I. Solomon, M. Sandgren, B. Kelemen, Chem. Rev. 2018, 118, 2593–2635.
- 3
- 3aP. Wu, J. Zhang, Q. Chen, W. Peng, B. Wang, Chin. J. Catal. 2022, 43, 913–927;
- 3bR. Trammell, K. Rajabimoghadam, I. Garcia-Bosch, Chem. Rev. 2019, 119, 2954–3031;
- 3cN. Gagnon, W. B. Tolman, Acc. Chem. Res. 2015, 48, 2126–2131.
- 4M. J. Appel, C. R. Bertozzi, ACS Chem. Biol. 2015, 10, 72–84.
- 5
- 5aT. Dierks, B. Schmidt, L. V. Borissenko, J. H. Peng, A. Preusser, M. Mariappan, K. von Figura, Cell 2003, 113, 435–444;
- 5bN. M. Hendrikse, A. Sandegren, T. Andersson, J. Blomqvist, Å. Makower, D. Possner, C. Su, N. Thalén, A. Tjernberg, U. Westermark, J. Rockberg, S. Svensson Gelius, P.-O. Syrén, E. Nordling, iScience 2021, 24, 102154.
- 6
- 6aI. S. Carrico, B. L. Carlson, C. R. Bertozzi, Nat. Chem. Biol. 2007, 3, 321–322;
- 6bT. Krüger, T. Dierks, N. Sewald, Biol. Chem. 2019, 400, 289–297.
- 7S. Banerjee, S. J. Muderspach, T. Tandrup, K. E. H. Frandsen, R. K. Singh, J. Ø Ipsen, C. Hernández-Rollán, M. H. H. Nørholm, M. J. Bjerrum, K. S. Johansen, L. Lo Leggio, Biomol. Eng. 2022, 12, 194.
- 8C. W. Koo, F. J. Tucci, Y. He, A. C. Rosenzweig, Science 2022, 375, 1287–1291.
- 9S. T. Prigge, B. A. Eipper, R. E. Mains, L. M. Amzel, Science 2004, 304, 864–867.
- 10
- 10aM. Meury, M. Knop, F. P. Seebeck, Angew. Chem. Int. Ed. 2017, 56, 8115–8119; Angew. Chem. 2017, 129, 8227–8231;
- 10bM. Knop, T. Q. Dang, G. Jeschke, F. P. Seebeck, ChemBioChem 2017, 18, 161–165;
- 10cM. J. Appel, K. K. Meier, J. Lafrance-Vanasse, H. Lim, C. L. Tsai, B. Hedman, K. O. Hodgson, J. A. Tainer, E. I. Solomon, C. R. Bertozzi, Proc. Natl. Acad. Sci. USA 2019, 116, 5370–5375.
- 11P. G. Holder, L. C. Jones, P. M. Drake, R. M. Barfield, S. Banas, G. W. de Hart, J. Baker, D. Rabuka, J. Biol. Chem. 2015, 290, 15730–15745.
- 12D. A. Miarzlou, F. Leisinger, D. Joss, D. Haussinger, F. P. Seebeck, Chem. Sci. 2019, 10, 7049–7058.
- 13M. Knop, P. Engi, R. Lemnaru, F. P. Seebeck, ChemBioChem 2015, 16, 2147–2150.
- 14F. Leisinger, D. A. Miarzlou, F. P. Seebeck, Angew. Chem. Int. Ed. 2021, 60, 6154–6159; Angew. Chem. 2021, 133, 6219–6224.
- 15
- 15aE. G. Kovaleva, J. D. Lipscomb, Science 2007, 316, 453–457;
- 15bJ. Cho, A. Karlsson, J. V. Parales, R. E. Parales, D. T. Gibson, H. Eklund, S. Ramaswamy, Science 2003, 299, 1039–1042;
- 15cC. H. Kjaergaard, M. F. Qayyum, S. D. Wong, F. Xu, G. R. Hemsworth, D. J. Walton, N. A. Young, G. J. Davies, P. H. Walton, K. S. Johansen, K. O. Hodgson, B. Hedman, E. I. Solomon, Proc. Natl. Acad. Sci. USA 2014, 111, 8797–8802;
- 15dX. Li, W. T. Beeson, C. M. Phillips, M. A. Marletta, J. H. D. Cate, Structure 2012, 20, 1051–1061;
- 15eS. Kalita, S. Shaik, H. K. Kisan, K. D. Dubey, ACS Catal. 2020, 10, 11481–11492.
- 16The adopted QM/MM method employs DFT(B3LYP) for the QM part and AMBER force field for the MM part. See the Supporting Information for computational details.
- 17
- 17aR. E. Cowley, J. Cirera, M. F. Qayyum, D. Rokhsana, B. Hedman, K. O. Hodgson, D. M. Dooley, E. I. Solomon, J. Am. Chem. Soc. 2016, 138, 13219–13229;
- 17bH. Lim, M. L. Baker, R. E. Cowley, S. Kim, M. Bhadra, M. A. Siegler, T. Kroll, D. Sokaras, T.-C. Weng, D. R. Biswas, D. M. Dooley, K. D. Karlin, B. Hedman, K. O. Hodgson, E. I. Solomon, Inorg. Chem. 2020, 59, 16567–16581.
- 18S. Kim, J. Ståhlberg, M. Sandgren, R. S. Paton, G. T. Beckham, Proc. Natl. Acad. Sci. USA 2014, 111, 149–154.
- 19
- 19aA. Kunishita, M. Kubo, H. Sugimoto, T. Ogura, K. Sato, T. Takui, S. Itoh, J. Am. Chem. Soc. 2009, 131, 2788–2789;
- 19bJ. S. Woertink, L. Tian, D. Maiti, H. R. Lucas, R. A. Himes, K. D. Karlin, F. Neese, C. Würtele, M. C. Holthausen, E. Bill, J. Sundermeyer, S. Schindler, E. I. Solomon, Inorg. Chem. 2010, 49, 9450–9459;
- 19cA. Kunishita, M. Z. Ertem, Y. Okubo, T. Tano, H. Sugimoto, K. Ohkubo, N. Fujieda, S. Fukuzumi, C. J. Cramer, S. Itoh, Inorg. Chem. 2012, 51, 9465–9480;
- 19dJ. W. Ginsbach, R. L. Peterson, R. E. Cowley, K. D. Karlin, E. I. Solomon, Inorg. Chem. 2013, 52, 12872–12874.
- 20
- 20aJ. P. Klinman, Chem. Rev. 1996, 96, 2541–2562;
- 20bJ. W. Whittaker, Chem. Rev. 2003, 103, 2347–2363.
- 21
- 21aJ. M. Bollinger, C. Krebs, Curr. Opin. Chem. Biol. 2007, 11, 151–158;
- 21bD. A. Quist, D. E. Diaz, J. J. Liu, K. D. Karlin, JBIC J. Biol. Inorg. Chem. 2017, 22, 253–288;
- 21cJ. P. Klinman, J. Biol. Chem. 2006, 281, 3013–3016;
- 21dS. Y. Quek, S. Debnath, S. Laxmi, M. van Gastel, T. Krämer, J. England, J. Am. Chem. Soc. 2021, 143, 19731–19747.
- 22
- 22aR. Poli, J. N. Harvey, Chem. Soc. Rev. 2003, 32, 1–8;
- 22bK. Yoshizawa, Bull. Chem. Soc. Jpn. 2013, 86, 1083–1116;
- 22cM. Filatov, S. Shaik, J. Phys. Chem. A 1998, 102, 3835–3846;
- 22dD. Danovich, S. Shaik, J. Am. Chem. Soc. 1997, 119, 1773–1786.
- 23I. G. Denisov, Y. V. Grinkova, B. J. Baas, S. G. Sligar, J. Biol. Chem. 2006, 281, 23313–23318.
- 24S. Álvarez-Barcia, J. Kästner, Eur. Phys. J. Spec. Top. 2019, 227, 1657–1664.
This is the
German version
of Angewandte Chemie.
Note for articles published since 1962:
Do not cite this version alone.
Take me to the International Edition version with citable page numbers, DOI, and citation export.
We apologize for the inconvenience.
