Controlled protonation of iron-molybdenum cofactor by nitrogenase: a structural and theoretical analysis

Qualitative molecular modelling has been used to identify possible routes f or transfer of protons from the surface of the nitrogenase protein to the i ron-molybdenum cofactor (FeMoco) and to substrates during catalysis. Three proton-transfer routes have been identified; a water-fined channel running from the protein exterior to the homocitrate ligand of FeMoco, and two hydr ogen-bonded chains to specific FeMoco sulphur atoms. It is suggested that t he water channel is used for multiple proton deliveries to the substrate, a s well as in diffusion of products and substrates between FeMoco and the bu lk solvent, whereas the two hydrogen-bonded chains each allow a single prot on to be added to, and subsequently depart from, FeMoco during the catalyti c cycle. Possible functional differences in the proton-transfer channels ar e discussed in terms of assessment of the protein environment and specific hydrogen-bonding effects. The implications of these observations are discus sed in terms of the suppression of wasteful production of dihydrogen by nit rogenase and the Lowe-Thorneley scheme for dinitrogen reduction.