FeMocofactor

FeMo cofactor, often referred to as FeMo-co, is the active metallocluster of the Mo-dependent nitrogenase enzyme that catalyzes the biological reduction of atmospheric nitrogen (N2) to ammonia (NH3). It resides within the MoFe protein component of nitrogenase and plays a central role in the enzyme’s catalytic cycle, working in concert with the accompanying Fe protein which delivers electrons.

The cofactor is a complex metal-sulfur cluster with the composition Fe7MoS9C, containing seven iron atoms, one molybdenum atom, nine sulfur atoms, and a central interstitial carbon atom. A homocitrate ligand coordinates to molybdenum, helping to stabilize the cluster within the protein matrix. The cluster spans roughly a nanometer and is one of the most intricate metal-containing cofactors known in biology. Its detailed structure has been elucidated through X-ray crystallography and various spectroscopic methods.

Functionally, FeMo-co is believed to provide the active site where nitrogen binding and reduction occur. Electrons are supplied from the Fe protein in an ATP-dependent manner, enabling multi-electron, multi-proton transfers that convert N2 to NH3. While the exact sequence of substrate binding and intermediate states remains a subject of ongoing research, the cofactor is universally regarded as essential for the catalytic versatility of nitrogenase.

Biosynthesis and maturation involve a dedicated gene cluster and scaffold proteins that assemble the cofactor before its insertion into the MoFe protein. This assembly pathway includes multiple steps and auxiliary proteins (notably NifB, NifEN, and related factors) that construct and insert FeMo-co, enabling the enzyme’s nitrogen-fixing activity. FeMo-co is highly oxygen-sensitive, reflecting the anaerobic nature of nitrogenase.