Putative reaction mechanism of nitrogenase after dissociation of a sulfide ligand

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Putative reaction mechanism of nitrogenase after dissociation of a sulfide ligand. / Cao, Lili; Ryde, Ulf.

In: Journal of Catalysis, Vol. 391, 01.09.2020, p. 247–259.

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T1 - Putative reaction mechanism of nitrogenase after dissociation of a sulfide ligand

AU - Cao, Lili

AU - Ryde, Ulf

PY - 2020/9/1

Y1 - 2020/9/1

N2 - We have investigated the implications of the recent crystallographic findings that the m2-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 dis- sociated, 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 pro- duct 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.

AB - We have investigated the implications of the recent crystallographic findings that the m2-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 dis- sociated, 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 pro- duct 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.

KW - Nitrogenase

KW - QM/MM

KW - S2B dissociation

KW - Nitrogen fixation

KW - Alternating or distal reaction mechanism

U2 - 10.1016/j.jcat.2020.08.028

DO - 10.1016/j.jcat.2020.08.028

M3 - Article

VL - 391

SP - 247

EP - 259

JO - Journal of Catalysis

JF - Journal of Catalysis

SN - 1090-2694

ER -