The coordination chemistry of the metalloenzyme nitrogenase is centered around its active site, which contains a unique metal cluster called the FeMo-cofactor FeMoco . The FeMoco is composed of seven iron Fe atoms, one molybdenum Mo atom, nine sulfur S atoms, and one carbon atom, forming a complex structure with the general formula [MoFe7S9C]. This metal cluster is coordinated to the nitrogenase protein through cysteine amino acid residues.The conversion of atmospheric nitrogen N2 into ammonia NH3 by nitrogenase is a critical process in the global nitrogen cycle, as it allows the biologically unavailable N2 to be transformed into a form that can be utilized by living organisms. This process, known as nitrogen fixation, occurs through a series of complex electron transfer and bond-breaking/formation steps.The nitrogenase enzyme functions as a two-component system, consisting of the Fe protein also known as dinitrogenase reductase and the MoFe protein also known as dinitrogenase . The Fe protein contains a [4Fe-4S] cluster and is responsible for transferring electrons to the MoFe protein, which houses the FeMoco active site.The conversion of N2 to NH3 by nitrogenase proceeds through the following steps:1. ATP-dependent electron transfer: The Fe protein binds to ATP and receives an electron from a reducing agent such as ferredoxin or flavodoxin . The Fe protein then forms a complex with the MoFe protein, and the electron is transferred to the FeMoco active site. This process is repeated multiple times, with each electron transfer being accompanied by the hydrolysis of one ATP molecule.2. N2 binding and reduction: After the FeMoco active site has accumulated sufficient electrons, N2 binds to the FeMoco, replacing an interstitial carbide atom. The bound N2 molecule is then reduced through a series of proton-coupled electron transfer steps, which involve the breaking of the NN triple bond and the formation of new N-H bonds. This process ultimately generates two molecules of NH3.3. Product release and enzyme turnover: The produced NH3 molecules are released from the active site, and the nitrogenase enzyme returns to its initial state, ready for another round of N2 reduction.The unique coordination chemistry of the FeMoco active site in nitrogenase enables the enzyme to overcome the significant kinetic and thermodynamic barriers associated with N2 reduction. The Fe and Mo atoms in the FeMoco cluster are believed to facilitate the activation and reduction of N2 by providing multiple electron-rich sites that can stabilize the various nitrogen reduction intermediates. Additionally, the sulfur atoms in the FeMoco cluster may play a role in the protonation steps during N2 reduction. Overall, the intricate coordination environment of the FeMoco active site allows nitrogenase to perform the challenging task of converting atmospheric N2 into biologically available NH3.