The Metalloproteins group focuses on the structure-function relationships of metalloproteins and, specifically in this study, on the biosynthesis mechanisms of the [FeFe] hydrogenase active site. These enzymes efficiently catalyze the reversible oxidation of molecular hydrogen. They use an organometallic center termed H-cluster, whose physicochemical and structural properties serve as inspiration for developing catalysts aimed at a greater use of molecular hydrogen as a renewable energy source.
The H-cluster consists of a [Fe4S4] center linked to a binuclear iron center [2Fe]H, which is the actual site of hydrogen binding and transformation. The [2Fe]H biosynthesis requires the coordinated action of at least three accessory metalloproteins : HydF, HydE, and HydG, and involves radical chemistry. The HydG protein is responsible for producing cyanide and carbon monoxide ligands from L-tyrosine, in the form of an organometallic complex known as complex-B. This complex then serves as a substrate for the HydE protein, whose reaction and product remain unknown. The HydF protein acts as a scaffold on which the [2Fe]H center is constructed before being inserted into the hydrogenase.
Here, we used the HydE protein as a nano-cage to protect and then analyze the complex B produced by the HydG protein through crystallography. We also studied the transfer mode of this compound, which is highly unstable in an aqueous environment. We demonstrated that there is a direct and transient interaction between the HydG and HydE proteins, allowing a secure transfer of complex B and preventing its degradation. The mechanisms controlling this transfer are now under investigation.
Maturation of the [FeFe]-Hydrogenase : Direct Transfer of the (κ3-cysteinate)FeII(CN)(CO)2 Complex-B from HydG to HydE. Juneina Omeiri, Lydie Martin, Anthony Usclat, Mickael V. Cherrier, and Yvain Nicolet. Angewandte Chemie International Edition 2023, e202314819.
Contact : Yvain Nicolet, Metalloproteins Group (IBS/METALLO)