The mechanism of cysteine oxygenation by cysteine dioxygenase enzymes
The mechanism of cysteine oxygenation by cysteine dioxygenase enzymes
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DOI：
10.1021/ja0758178
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发表时间：
2007-12-05
影响因子：
15
通讯作者：
de Visser, Sam P.
中科院分区：
文献类型：
--
作者：
Aluri, Swathi;de Visser, Sam P.
我们在这里提出的第一个密度泛函理论研究半胱氨酸双加氧酶模型的半胱氨酸双加氧的机制。一个大的活性位点模型包含的配体结合到铁加氨基酸残基，参与与基板的氢键相互作用。该反应通过竞争单重态、三重态和五重态自旋态的多状态反应模式发生，其中后者是大多数复合物中的基态。预测了几个新的中间体，这是以前没有预料到的。双氧结合的复合物处于单重自旋基态，并且与五重自旋态交叉的状态导致FeOOS环结构，该FeOOS环结构分裂成半胱氨酰氧化物自由基，该半胱氨酰氧化物自由基从铁中心重新取向并提取电子。在最后一步中，氧代铁将氧原子提供给底物，以在高度放热的过程中产生半胱氨酸亚磺酸。速率决定步骤是五重态表面上反应机制的初始步骤。
We present here the first density functional theoretic study into the mechanism of cysteine dioxygenation by a model of cysteine dioxygenase enzymes. A large active site model containing the ligands bound to iron plus amino acid residues that are involved in hydrogen bonding interactions with the substrate is used. The reaction takes place via multi-state reactivity patterns on competing singlet, triplet, and quintet spin states, whereby the latter is the ground state in most complexes. Several new intermediates have been predicted, which have not been anticipated before. The dioxygen-bound complex is in a singlet spin ground state, and a state crossing to the quintet spin state leads to an FeOOS ring structure that splits into a cysteinyloxide radical that reorients and abstracts an electron from the iron center. In the final step, the oxoiron donates the oxygen atom to the substrate to produce cysteine sulfinic acid in a highly exothermic process. The rate-determining step is the initial step in the reaction mechanism on the quintet spin state surface.