Putative reaction mechanism of nitrogenase after dissociation of a sulfide ligand
Putative reaction mechanism of nitrogenase after dissociation of a sulfide ligand
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DOI：
10.1016/j.jcat.2020.08.028
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发表时间：
2020-11-01
影响因子：
7.3
通讯作者：
Ryde, Ulf
中科院分区：
文献类型：
--
作者：
Cao, Lili;Ryde, Ulf
我们研究了最近晶体学发现的意义，即mu(2)-桥接S2B硫化物配体可以从氮酶的活性位点FeMo簇可逆地解离。我们结合量子力学和分子力学（QM/MM）计算表明，一旦S2B解离，N-2可能在该位置结合，并可以通过热力学有利的步骤质子化成两个NH3基团。底物与两个蛋白质配体Gln-191和His-195形成氢键。对于所有步骤，我们研究了His-195的三种可能的质子化状态（ND1、NE2或两者都是质子化状态）。我们发现热力学上有利的路径包括端对NNH2结构、端对/端对混合h2nnhh结构、端对H2NNH2结构、桥接NH2结构和桥接NH3结构。在所有情况下，His-195似乎都在NE2原子上质子化了。NH3产物的解离通常是不利的，需要进一步还原或质子化簇或重新结合S2B。综上所述，我们的计算表明，S2B的解离产生了Fe2和Fe6原子之间的天然结合和反应位点，这可以支持具有有利能量学的交替反应机制。(C) 2020作者。Elsevier Inc.出版。
We have investigated the implications of the recent crystallographic findings that the mu(2)-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, N-2 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. (C) 2020 The Author(s). Published by Elsevier Inc.