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The oxidative inactivation of FeFe hydrogenase reveals the flexibility of the H-cluster

Nature Chemistry volume 6, pages 336–342 (2014)Cite this article

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An Author Correction to this article was published on 24 September 2019

Abstract

Nature is a valuable source of inspiration in the design of catalysts, and various approaches are used to elucidate the mechanism of hydrogenases, the enzymes that oxidize or produce H2. In FeFe hydrogenases, H2 oxidation occurs at the H-cluster, and catalysis involves H2 binding on the vacant coordination site of an iron centre. Here, we show that the reversible oxidative inactivation of this enzyme results from the binding of H2 to coordination positions that are normally blocked by intrinsic CO ligands. This flexibility of the coordination sphere around the reactive iron centre confers on the enzyme the ability to avoid harmful reactions under oxidizing conditions, including exposure to O2. The versatile chemistry of the diiron cluster in the natural system might inspire the design of novel synthetic catalysts for H2 oxidation.

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Figure 1: Structure of the H-cluster.
Figure 2: Chronoamperometric data obtained with a film of Cr hydrogenase covalently attached to a rotating graphite electrode.
Figure 3: Rate constants for the inactivation/reactivation processes determined from electrochemical experiments.
Figure 4: Thermal fluctuations of Dd FeFe hydrogenase Phe296 probed by MD.
Figure 5: States of the active sites involved in catalysis (within the green triangle) and in high-potential inactivation.
Figure 6: Structures of 1H2 and 2H2, as predicted by DFT calculations.

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Acknowledgements

The authors thank S. Dementin for helpful discussions and critical reading of the manuscript. The authors acknowledge funding from Centre National de la Recherche Scientifique, Aix-Marseille Université and Agence Nationale de la Recherche (ANR-12-BS08-0014 and ANR-2010-BIOE-004). L.D.G. acknowledges support from Ministero dell'Istruzione, dell'Università e della Ricerca (Prin 2010M2JARJ). P.W. acknowledges the Ministry of Education, Republic of China (Taiwan) for a PhD scholarship, and J.B. acknowledges the Engineering and Physical Sciences Research Council, grant EP/J015571/1, and the Royal Society for a University Research Fellowship. The UK's High Performance Computing Materials Chemistry Consortium (funded by the Engineering and Physical Sciences Research Council, EP/ F067496) is acknowledged for access to the high-performance computing facility HECToR.

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Authors and Affiliations

  1. Aix Marseille Université, CNRS, BIP UMR 7281, Marseille, 13402, France

    Vincent Fourmond, Carole Baffert, Pierre Ezanno & Christophe Léger

  2. Department of Earth and Environmental Science, Università degli Studi di Milano-Bicocca, P.zza della Scienza 1, Milan, 20126, Italy

    Claudio Greco & Maurizio Bruschi

  3. iBiTec-S, SB2SM, LMB (UMR CNRS 8221), DSV, CEA, Gif-sur-Yvette, 91191, France

    Kateryna Sybirna & Hervé Bottin

  4. Université de Toulouse, INSA, UPS, INP, LISBP, INRA:UMR792,135 CNRS:UMR 5504, avenue de Rangueil, Toulouse, 31077, France

    Isabelle Meynial-Salles & Philippe Soucaille

  5. Department of Physics and Astronomy, University College London, Gower Street, London, WC1E 6BT, UK

    Po-Hung Wang, Marco Montefiori & Jochen Blumberger

  6. Department of Biotechnology and Biosciences, Università degli Studi di Milano-Bicocca, P.zza della Scienza 2, Milan, 20126, Italy

    Luca De Gioia

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Contributions

V.F., C.G., C.B., J.B., L.D.G. and C.L. designed the experiments. V.F., C.G., P-H.W., P.E., M.M. and M.B. performed the experiments. V.F., C.G., J.B., L.D.G. and C.L. analysed the data. K.S. and H.B. provided the enzyme from Cr and constructed the mutants. I.M-S. and P.S. provided the enzyme from Ca. V.F., C.G., C.B., J.B., L.D.G. and C.L. co-wrote the paper.

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Correspondence to Vincent Fourmond.

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Fourmond, V., Greco, C., Sybirna, K. et al. The oxidative inactivation of FeFe hydrogenase reveals the flexibility of the H-cluster. Nature Chem 6, 336–342 (2014). https://doi.org/10.1038/nchem.1892

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