Local Electric Fields as a Natural Switch of Heme-Iron Protein Reactivity.
Local Electric Fields as a Natural Switch of Heme-Iron Protein Reactivity.
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DOI：
10.1021/acscatal.1c00687
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发表时间：
2021-06-04
期刊：
影响因子：
12.9
通讯作者：
Alexandrova AN
中科院分区：
文献类型：
--
作者：
Bím D;Alexandrova AN
血红素-铁氧化还原酶通过高价FeIVO中间体进行关键和复杂的转化，如非活性饱和烃的氧化。这些酶具有相同的铁配位，只是轴向连接不同，例如P450加氧酶中的Cys，过氧化氢酶中的Tyr和过氧化物酶中的His。通过对200个血红素-铁蛋白的检测，我们发现蛋白质宿主在活性部位上施加了高度特异的分子内电场，而且电场的方向和大小与蛋白质的功能有很强的相关性。在所有的血红素蛋白中，磁场优先与Fe-O键(Fz)对齐。Cys连接的P450加氧酶的平均Fz最高，为28.5mV cm−1，即最能增强氧基的氧自由基特性，并与这些蛋白激活强C-H键的能力一致。相反，在酪氨酸连接的蛋白质中，平均Fz仅为3.0mV cm−1，明显抑制单电子的离路氧化，而在组氨酸连接的蛋白质中，Fz为8.7mV cm−1。作用场范围是在较负的Fz处的低反应活性与较正的Fz处的低选择性之间的权衡所给出的。因此，一个被放置在另一个血红素-铁蛋白类别特有的领域的血红素-铁位点失去了它的典型功能，而获得了一个不利的功能。因此，蛋白质支架产生的电场，加上轴向配体的性质，控制着所有的血红素-铁化学。
Heme-iron oxidoreductases operating through the high-valent FeIVO intermediates perform crucial and complicated transformations, such as oxidations of unreactive saturated hydrocarbons. These enzymes share the same Fe coordination, only differing by the axial ligation, e.g., Cys in P450 oxygenases, Tyr in catalases, and His in peroxidases. By examining ~200 heme-iron proteins, we show that the protein hosts exert highly specific intramolecular electric fields on the active sites, and there is a strong correlation between the direction and magnitude of this field and the protein function. In all heme proteins, the field is preferentially aligned with the Fe–O bond (Fz). The Cys-ligated P450 oxygenases have the highest average Fz of 28.5 MV cm−1, i.e., most enhancing the oxyl-radical character of the oxo group, and consistent with the ability of these proteins to activate strong C–H bonds. In contrast, in Tyr-ligated proteins, the average Fz is only 3.0 MV cm−1, apparently suppressing single-electron off-pathway oxidations, and in His-ligated proteins, Fz is −8.7 MV cm−1. The operational field range is given by the trade-off between the low reactivity of the FeIVO Compound I at the more negative Fz, and the low selectivity at the more positive Fz. Consequently, a heme-iron site placed in the field characteristic of another heme-iron protein class loses its canonical function, and gains an adverse one. Thus, electric fields produced by the protein scaffolds, together with the nature of the axial ligand, control all heme-iron chemistry.
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