N2H2 binding to the nitrogenase FeMo cluster studied by QM/MM methods
N2H2 binding to the nitrogenase FeMo cluster studied by QM/MM methods
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DOI：
10.1007/s00775-020-01780-5
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发表时间：
2020-04-07
影响因子：
3
通讯作者：
Ryde, Ulf
中科院分区：
文献类型：
--
作者：
Cao, Lili;Ryde, Ulf
本文对固氮酶N-2束缚态的可能结构进行了系统的量子力学和分子力学相结合的研究。我们假设N-2立即质子化为N2 H2状态，从而避免了确定质子在团簇中位置的问题。我们系统地研究了端对和侧对结构，以及HNNH和NNH 2态。我们的研究结果表明，N2 H2的结合更多地取决于与周围蛋白质的相互作用和空间冲突，而不是由配体和簇的内在偏好。TPSS和B3 LYP密度泛函理论方法的最佳结合模式具有反式-HNNH末端结合到Fe 2。它通过将底物与His-195和Ser-278堆叠而稳定。然而，至少在一些计算中，其他几种结构在能量上相当接近（在3-35 kJ/mol内）：与Fe 2末端结合的相应的顺式-HNNH结构在B3 LYP中是第二好的。具有HNNH 2末端结合到Fe 6的结构对于TPSS是第二最稳定的（其中第三个质子从高柠檬酸配体转移到底物）。反式-HNNH与Fe 4或Fe 6结合，或顺式-HNNH与Fe 6结合的结构也相当稳定。最后，与TPSS功能，结构与顺式-HNNH侧上结合到簇的Fe 3-Fe 4-Fe 5-Fe 7面也是相当低的能量，但所有侧上的结构是强烈不利的B3 LYP方法。
We have made a systematic combined quantum mechanical and molecular mechanical (QM/MM) investigation of possible structures of the N-2 bound state of nitrogenase. We assume that N-2 is immediately protonated to a N2H2 state, thereby avoiding the problem of determining the position of the protons in the cluster. We have systematically studied both end-on and side-on structures, as well as both HNNH and NNH2 states. Our results indicate that the binding of N2H2 is determined more by interactions and steric clashes with the surrounding protein than by the intrinsic preferences of the ligand and the cluster. The best binding mode with both the TPSS and B3LYP density-functional theory methods has trans-HNNH terminally bound to Fe2. It is stabilised by stacking of the substrate with His-195 and Ser-278. However, several other structures come rather close in energy (within 3-35 kJ/mol) at least in some calculations: The corresponding cis-HNNH structure terminally bound to Fe2 is second best with B3LYP. A structure with HNNH2 terminally bound to Fe6 is second most stable with TPSS (where the third proton is transferred to the substrate from the homocitrate ligand). Structures with trans-HNNH, bound to Fe4 or Fe6, or cis-HNNH bound to Fe6 are also rather stable. Finally, with the TPSS functional, a structure with cis-HNNH side-on binding to the Fe3-Fe4-Fe5-Fe7 face of the cluster is also rather low in energy, but all side-on structures are strongly disfavoured by the B3LYP method.