Mechanism of dioxygen activation in 2-oxoglutarate-dependent enzymes: A hybrid DFT study
Mechanism of dioxygen activation in 2-oxoglutarate-dependent enzymes: A hybrid DFT study
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DOI：
10.1002/chem.200305306
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发表时间：
2004-02-20
影响因子：
4.3
通讯作者：
Siegbahn, PEM
中科院分区：
文献类型：
--
作者：
Borowski, T;Bassan, A;Siegbahn, PEM
用杂化密度泛函理论研究了2-酮戊二酸依赖酶中分子氧活化的反应机理。这里报道的结果支持一种机制，其中所有的化学转化发生在一个五重势能面。更具体地，活化的双氧物质攻击共底物的羰基，产生Fe-II-过琥珀酸盐-CO2络合物，其容易释放二氧化碳分子。其中形成的Fe-II-过酸-CO2络合物的步骤被发现是限速的和不可逆的。随后的铁-II-过琥珀酸盐复合物中的O-O键的异裂解在两个单电子步骤中进行，并产生高价铁-氧代物种Fe-IV=O，这最有可能是负责由2-酮戊二酸依赖性酶催化的氧化反应。同时O-O和C-C键断裂的协调途径的七重势能面被发现是不太有利的。不同形式的活性铁氧物种的相对稳定性进行了评估，五重五配位络合物被认为是最稳定的。
The reaction mechanism for dioxygen activation in 2-oxoglutarate-dependent enzymes has been studied by means of hybrid density functional theory. The results reported here support a mechanism in which all chemical transformations take place on a quintet potential-energy surface. More specifically, the activated dioxygen species attacks the carbonyl group of the co-substrate producing the Fe-II-persuccinate-CO2 complex, which readily releases the carbon dioxide molecule. The step in which the Fe-II-peracid-CO2 complex is formed is found to be rate-limiting and irreversible. Subsequent heterolysis of the O-O bond in the Fe-II-persuccinate complex proceeds in two one-electron steps and produces the high-valent iron-oxo species Fe-IV=O, which is most likely to be responsible for oxidative reactions catalyzed by 2-oxoglutarate-dependent enzymes. The concerted pathway for simultaneous O-O and C-C bond cleavage on the septet potential-energy surface is found to be less favorable. The relative stability of different forms of the active iron-oxo species is assessed, and the quintet five-coordinate complex is found to be most stable.