Does the environment around the H-cluster allow coordination of the pendant amine to the catalytic iron center in [FeFe] hydrogenases? Answers from theory
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[FeFe] hydrogenases are H2-evolving enzymes that feature a diiron cluster in their active site (the [2Fe]H cluster). One of the iron atoms has a vacant coordination site that directly interacts with H2, thus favoring its splitting in cooperation with the secondary amine group of a neighboring, flexible azadithiolate ligand. The vacant site is also the primary target of the inhibitor O2. The [2Fe]H cluster can span various redox states. The active-ready form (Hox) attains the FeIIFeI state. States more oxidized than Hox were shown to be inactive and/or resistant to O2. In this work, we used density functional theory to evaluate whether azadithiolate-to-iron coordination is involved in oxidative inhibition and protection against O2, a hypothesis supported by recent results on biomimetic compounds. Our study shows that Fe–N(azadithiolate) bond formation is favored for an FeIIFeII active-site model which disregards explicit treatment of the surrounding protein matrix, in line with the case of the corresponding FeIIFeII synthetic system. However, the study of density functional theory models with explicit inclusion of the amino acid environment around the [2Fe]H cluster indicates that the protein matrix prevents the formation of such a bond. Our results suggest that mechanisms other than the binding of the azadithiolate nitrogen protect the active site from oxygen in the so-called H ox inact state.
KeywordsHydrogen Hydrogenases Density functional theory Iron–sulfur cluster
Financial support of this work from the Cluster of Excellence “Unifying Concepts in Catalysis” (Berlin) is gratefully acknowledged; We acknowledge the CINECA award under the ISCRA initiative, for the availability of high performance computing resources and support. C.L., F.V., and C.B. acknowledge the CNRS, Aix-Marseille Université, and the ANR (ANR-12-BS08-0014) for funding.
- 62.Greco C, Silakov A, Bruschi M, Ryde U, De Gioia L, Lubitz W (2011) Eur J Inorg Chem 2011:1043–1049. doi: 10.1002/ejic.201001058