Structural and Mechanistic Insights into CO2 Activation by Nitrogenase Iron Protein

The Fe protein of nitrogenase catalyzes the ambient reduction of CO₂ when its cluster is present in the all-ferrous, [Fe₄S₄]⁰ oxidation state. Here, we report a combined structural and theoretical study that probes the unique reactivity of the all-ferrous Fe protein toward CO₂. Structural comparisons of the Azotobacter vinelandii Fe protein in the [Fe₄S₄]⁰ and [Fe₄S₄]⁺ states point to a possible asymmetric functionality of a highly conserved Arg pair in CO₂ binding and reduction. Density functional theory (DFT) calculations provide further support for the asymmetric coordination of O by the “proximal” Arg and binding of C to a unique Fe atom of the all-ferrous cluster, followed by donation of protons by the proximate guanidinium group of Arg that eventually results in the scission of a C−O bond. These results provide important mechanistic and structural insights into CO₂ activation by a surface-exposed, scaffold-held [Fe₄S₄] cluster.