Electron transfer in nitrogenase catalysis

Nitrogenase is a two-component enzyme that catalyzes the nucleotide-dependent reduction of N2 to 2NH3. This process involves three redox-active metal-containing cofactors including a [4Fe–4S] cluster, an eight-iron P cluster and a seven-iron plus molybdenum FeMo-cofactor, the site of substrate reduction. A deficit-spending model for electron transfer has recently been proposed that incorporates protein conformational gating that favors uni-directional electron transfer among the metalloclusters for the activation of the substrate-binding site. Also reviewed is a proposal that each of the metal clusters cycles through only two redox states of the metal–sulfur core as the system accumulates the multiple electrons required for substrate binding and reduction. In particular, it was suggested that as FeMo-cofactor acquires the four electrons necessary for optimal binding of N2, each successive pair of electrons is stored as an Fe–H−–Fe bridging hydride, with the FeMo-cofactor metal-ion core retaining its resting redox state. We here broaden the discussion of stable intermediates that might form when FeMo-cofactor receives an odd number of electrons.

► The order of electron transfers between nitrogenase metal clusters is described. ► The core of each nitrogenase metal cluster cycles through a single redox couple. ► Hydrides bridging Fe ions of FeMo-cofactor ‘store’ reducing equivalents.