FeMoco

FeMoco, the iron-molybdenum cofactor, is the active site of the molybdenum-containing nitrogenase enzyme, which catalyzes the reduction of atmospheric nitrogen (N2) to ammonia (NH3) in certain bacteria and archaea. It resides in the MoFe protein component of nitrogenase and works in concert with the Fe protein, which delivers electrons in an ATP-dependent cycle.

The cofactor is a complex metal-sulfur cluster composed of seven iron atoms, one molybdenum atom, and nine sulfur atoms, arranged around a central interstitial carbon atom (carbide). A homocitrate ligand coordinates to the Mo atom, helping to anchor the cluster in the protein. The FeMo cofactor is connected to a separate P cluster that participates in electron transfer from the Fe protein to the cofactor, forming a conduit for multi-electron delivery to the substrate site.

Functionally, FeMoco is the site where N2 binding and its successive proton-coupled electron transfers occur, enabling the multi-step reduction of N2 to NH3. The overall nitrogenase reaction consumes ATP and electrons supplied by the Fe protein, and molecular hydrogen is produced as a byproduct. A widely cited overall equation for the Mo nitrogenase is N2 + 8 e− + 8 H+ + 16 ATP → 2 NH3 + H2 + 16 ADP + 16 Pi.

Discovery and context: the FeMo cofactor was characterized through structural and biochemical studies of the MoFe protein, with X-ray crystallography revealing its distinctive cluster containing Mo, Fe, S, and the central carbide. FeMoco is a defining feature of Mo-containing nitrogenase; other nitrogenases use variant cofactors, such as vanadium- or iron-only cofactors, but FeMoco remains central to Mo nitrogenase activity.