Elsevier

Journal of Catalysis

Volume 391, November 2020, Pages 247-259
Journal of Catalysis

Putative reaction mechanism of nitrogenase after dissociation of a sulfide ligand

https://doi.org/10.1016/j.jcat.2020.08.028Get rights and content
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Highlights

  • A reaction of nitrogenase with a dissociated S2B ligand is thermodynamically feasible.

  • It follows an alternating mechanism, with NNH2, HNNH2 and H2NNH2 as intermediates.

  • Dissociation of NH3 requires protonation or reduction of the FeMo cluster or rebinding of S2B.

Abstract

We have investigated the implications of the recent crystallographic findings that the µ2-bridging S2B sulfide ligand may reversibly dissociate from the active-site FeMo cluster of nitrogenase. We show with combined quantum mechanical and molecular mechanical (QM/MM) calculations that once S2B has dissociated, N2 may bind in that position and can be protonated to two NH3 groups by thermodynamically favourable steps. The substrate forms hydrogen bonds with two protein ligands, Gln-191 and His-195. For all steps, we have studied three possible protonation states of His-195 (protonated on either ND1, NE2 or both). We find that the thermodynamically favoured path involves an end-on NNH2 structure, a mixed side-on/end-on H2NNH structure, a side-on H2NNH2 structure, a bridging NH2 structure and a bridging NH3 structure. In all cases, His-195 seems to be protonated on the NE2 atom. Dissociation of the NH3 product is often unfavourable and requires either further reduction or protonation of the cluster or rebinding of S2B. In conclusion, our calculations show that dissociation of S2B gives rise to a natural binding and reaction site for nitrogenase, between the Fe2 and Fe6 atoms, which can support an alternating reaction mechanism with favourable energetics.

Keywords

Nitrogenase
QM/MM
S2B dissociation
Nitrogen fixation
Alternating or distal reaction mechanism

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