QM/MM MD simulations reveal an asynchronous PCET mechanism for nitrite reduction by copper nitrite reductase
QM/MM MD simulations reveal an asynchronous PCET mechanism for nitrite reduction by copper nitrite reductase
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QM/MM MD 模拟揭示了亚硝酸铜还原酶还原亚硝酸盐的异步 PCET 机制
DOI：
10.1039/d0cp03053h
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发表时间：
2020-09-28
影响因子：
3.3
通讯作者：
Wang, Binju
中科院分区：
文献类型：
--
作者：
Cheng, Ronny;Wu, Chun;Wang, Binju
亚硝酸盐还原酶是通过催化亚硝酸盐还原为一氧化氮气体来帮助反硝化过程的酶。由于该反应是涉及气体形成的第一个承诺步骤，因此它被认为是反硝化的重要步骤。然而，含铜亚硝酸盐还原酶的作用机制仍然存在争议，由于理论和实验数据之间的差异，特别是在二级壳残基Asp 98和His 255的作用和两个铜位点之间的电子转移机制。在此，我们重新审视了A.利用QM（B3 LYP）/MM为基础的代谢动力学方法对粪便亚硝酸铜还原酶进行了研究。发现T_1-Cu分子内电子转移是通过异步质子耦合电子转移（PCET）机制进行的，电子转移（ET）先于质子转移（PT）。特别是，我们发现ET过程是由Asp 98从看门人到近端的构象转换驱动的，这比PCET本身需要更多的能量。这些结果强调，包括电子供体是至关重要的调查电子转移相关的过程，如PCET。
Nitrite reductases are enzymes that aid in the denitrification process by catalyzing the reduction of nitrite to nitric oxide gas. Since this reaction is the first committed step that involves gas formation, it is regarded to be a vital step for denitrification. However, the mechanism of copper-containing nitrite reductase is still under debate due to the discrepancy between the theoretical and experimental data, especially in terms of the roles of secondary shell residues Asp98 and His255 and the electron transfer mechanism between the two copper sites. Herein, we revisited the nitrite reduction mechanism ofA. faecaliscopper nitrite reductase using QM(B3LYP)/MM-based metadynamics. It is found that the intramolecular electron transfer from T1-Cu to T2-Cu occursviaan asynchronous proton-coupled electron transfer (PCET) mechanism, with electron transfer (ET) preceding proton transfer (PT). In particular, we found that the ET process is driven by the conformation conversion of Asp98 from the gatekeeper to the proximal one, which is much more energy-demanding than the PCET itself. These results highlight that the inclusion of an electron donor is vital to investigate electron-transfer related processes such as PCET.