A De Novo Heterodimeric Due Ferri Protein Minimizes the Release of Reactive Intermediates in Dioxygen-Dependent Oxidation
A De Novo Heterodimeric Due Ferri Protein Minimizes the Release of Reactive Intermediates in Dioxygen-Dependent Oxidation
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DOI：
10.1002/anie.201707637
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发表时间：
2017-12-04
影响因子：
16.6
通讯作者：
Lombardi, Angela
中科院分区：
文献类型：
--
作者：
Chino, Marco;Leone, Linda;Lombardi, Angela
金属蛋白利用 O-2 作为氧化剂，通常可以在不释放 H2O2 或氧自由基的情况下实现 4 电子还原。几种蛋白质已被设计用于催化一电子或二电子氧化化学，但催化 O-2 净 4 电子还原的蛋白质的从头设计尚未报道。我们报告了通过点击化学构建的二铁结合四螺旋束，该四螺旋束由两个不同的共价连接的（2）单体组成。令人惊讶的是，原型蛋白 DF-C1 与早期 DF（DF：二铁，二铁）的反应性存在很大差异。在 O-2 存在的情况下，DF 在 4-氨基苯酚的氧化过程中释放醌亚胺和游离 H2O2，而 Fe-III-DF-C1 将醌亚胺隔离到活性位点中，并在支架内部催化氧化和还原的 4-氨基苯酚之间的氧化偶联。支架的不对称性允许对底物结合袋进行精细设计，从而确保选择性。
Metalloproteins utilize O-2 as an oxidant, and they often achieve a 4-electron reduction without H2O2 or oxygen radical release. Several proteins have been designed to catalyze one or two-electron oxidative chemistry, but the de novo design of a protein that catalyzes the net 4-electron reduction of O-2 has not been reported yet. We report the construction of a diiron-binding four-helix bundle, made up of two different covalently linked (2) monomers, through click chemistry. Surprisingly, the prototype protein, DF-C1, showed a large divergence in its reactivity from earlier DFs (DF: due ferri, two iron). DFs release the quinone imine and free H2O2 in the oxidation of 4-aminophenol in the presence of O-2, whereas Fe-III-DF-C1 sequesters the quinone imine into the active site, and catalyzes inside the scaffold an oxidative coupling between oxidized and reduced 4-aminophenol. The asymmetry of the scaffold allowed a fine-engineering of the substrate binding pocket, that ensures selectivity.