Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056, Basel, Switzerland.
Angew Chem Int Ed Engl. 2016 Aug 16;55(34):10126-30. doi: 10.1002/anie.201604552. Epub 2016 Jul 13.
Nitric oxide binding and unbinding from myoglobin (Mb) is central to the function of the protein. By using reactive molecular dynamics (MD) simulations, the dynamics following NO dissociation were characterized in both time and space. Ligand rebinding can be described by two processes on the 10 ps and 100 ps timescale, which agrees with recent optical and X-ray absorption experiments. Explicitly including the iron out-of-plane (Fe-oop) coordinate is essential for a meaningful interpretation of the data. The proposed existence of an "Fe-oop/NO-bound" state is confirmed and assigned to NO at a distance of approximately 3 Å away from the iron atom. However, calculated XANES spectra suggest that it is diffcult to distinguish between NO close to the heme-Fe and positions further away in the primary site. Another elusive state, with Fe-ON coordination, was not observed experimentally because it is masked by the energetically more favorable but dissociative (4) A state in this region, which makes the Fe-ON local minimum unobservable in wild-type Mb. However, suitable active-site mutations may stabilize this state.
一氧化氮与肌红蛋白（Mb）的结合和解离对蛋白质的功能至关重要。通过使用反应分子动力学（MD）模拟，从时间和空间两个方面描述了 NO 解离后的动力学。配体的重新结合可以用 10 ps 和 100 ps 时间尺度上的两个过程来描述，这与最近的光学和 X 射线吸收实验结果一致。明确包括铁出平面（Fe-oop）坐标对于对数据进行有意义的解释是必不可少的。提出了“Fe-oop/NO 结合”态的存在，并将其分配给与铁原子距离约为 3 Å 的 NO。然而，计算的 XANES 谱表明，很难区分靠近血红素-Fe 的 NO 和在主位中更远的位置。另一个难以捉摸的状态，具有 Fe-ON 配位，在实验中没有观察到，因为在该区域中，具有更高能量但解离的（4）A 态使 Fe-ON 局部最小值在野生型 Mb 中不可见，从而掩盖了该状态。然而，合适的活性位点突变可能会稳定这种状态。
