Activated [Fe]-hydrogenase structure

Hydrogen gas (H2) is a clean energy carrier for future. Hydrogenases catalyses production and consumption of H2 and provides an excellent template to synthesize new robust H2-activtion/production catalysts for H2-based energy technologies. The precise structure of the active sites and its catalytic mechanism are required as a template for the design of new biomimetic catalysts.

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Jun 17, 2019
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[Fe]-hydrogenase is involved in the methanogenesis from H2 and CO2. This enzyme contains the iron-guanylylpyridinol (FeGP) cofactor at the active sites. A decade ago, our group has reported the crystal structure of [Fe]-hydrogenase in an open-inactive form [1]. Based on this finding, several catalytic mechanisms of this enzyme were proposed and in recent years, many mimic models of the FeGP cofactor were chemically synthesized. However, to get clear picture of the catalytic mechanism, the protein complex with the substrate is required.


After 10-years efforts, we reported the atomic-resolution (1.06 Å) structure of [Fe]-hydrogenase bound with substrate, in which the activated enzyme is ready for H2-activation at the mono-iron site [2,3]. The active-sites cleft closed and the water ligand of the Fe site is kicked out from the Fe centre, which results in a penta-coordinated Fe form. The removal of the water ligand makes the open Fe site for the H2 binding. The structural change was supported by Mössbauer and infrared spectroscopic analyses. Now, we can answer the long-term question based on this structural data, why [Fe]-hydrogenase does not catalyse H2-cleavage in the absence of methenyl-H4MPT+ substrate. The methenyl-H4MPT+ substrate functioned not only as the hydride acceptor but also performed to close the active-sites and to activate the Fe centre. QM/MM computations based on the active-structural models indicate that the deprotonated 2-OH group on the FeGP cofactor worked as the catalytic base; H2-binding, H2-cleavage and hydride transfer proceed smoothly in the active site. Interestingly, in the catalytic cycle, the substrate is distorted, repositioned and relaxed to perform the reactions. Base on structural analyses, we show the precise structure of the Fe centre as well as illustrate the catalytic cycle of the [Fe]-hydrogenase. We believe that our finding can offer useful information for the design of new H2-activation/generation catalysts.

 

For more detail information, see our article "The atomic-resolution crystal structure of activated [Fe]-hydrogenase" in Nature Catalysis [2].

   
[1]  Shima, S., Pilak, O., Vogt, S., Schick, M., Stagni, M.S., Meyer-Klaucke, W., Warkentin, E., Thauer, R.K., Ermler, U. The crystal structure of [Fe]-hydrogenase reveals the geometry of the active site. Science 321, 572-575 (2008).

[2] Huang, G., Wagner, T., Wodrich, M.D., Ataka, K., Bill, E., Ermler, U., Hu, X., Shima, S. The atomic-resolution crystal structure of activated [Fe]-hydrogenase. Nature Catalysis 2, 537–543 (2019) https://doi.org/10.1038/s41929-019-0289-4.

[3] Nicolet, Y. How [Fe]-hydrogenase metabolizes dihydrogen. Nature Catalysis 2, 481–482 (2019).

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Seigo Shima

Research Group Leader, Max Planck Institute for Terrestrial Microbiology

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