Active-site stereochemical control of oxygen atom transfer reactivity in sulfite oxidase
Active-site stereochemical control of oxygen atom transfer reactivity in sulfite oxidase
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DOI：
10.1021/ja017217t
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发表时间：
2002-08-07
影响因子：
15
通讯作者：
Kirk, ML
中科院分区：
文献类型：
--
作者：
Peariso, K;McNaughton, RL;Kirk, ML
最近报道了一些对称的六配位二氧钼(VI)络合物的实验和计算研究，以此作为钼杂蝶呤酶亚硫酸盐氧化酶(SO)完全氧化形式的模型。这些研究表明，SO中的两个末端氧供体在电子上是等价的。然而，SO中具有催化活性的Mo(VI)活性中心的共有结构是五配位的正方形锥体，具有两个末端氧供体、一个烯-1，2-二硫代络合物和一个半胱氨酸硫供体配体。在密度泛函理论水平上对SO活性中心[Mo(VI)O2(S2C2Me2)(SCH3)]-在C1对称性中的最小模型进行了计算研究，以计算LUMO的组成，它是与亚硫酸盐底物的氧原子转移(OAT)反应中假定的电子受体轨道。该模型中的LUMO主要由Mo与赤道氧(Oeq)之间的MoDxy−pπ*相互作用组成，而轴向氧(OAx)对该轨道没有贡献。事实上，具有大量Oax性的LUMO+1轨道的能量比LUMO高出近1 eV。在酶催化过程中，OAX-−、Mo-−、−-C扭转角的变化可能有助于OEQ的选择。进行了计算，其中该扭转角度变化了20°到360°。这些计算表明，MoDxy−Oeqpπ*相互作用，因此OeqATOM特征，总是主导着LUMO。这些结果表明，氧原子的选择和活化是氧化的SO活性中心的低对称性结构的直接函数，并通过其对赤道氧供体的动力学反式效应为烯-1，2-二硫代硫酸酯提供了促进OAT反应活性的作用。
A number of both experimental and computational studies have recently been reported for symmetric, six-coordinate dioxomolybdenum(VI) complexes as models of the fully oxidized form of the molybdopterin enzyme sulfite oxidase (SO). Such studies have suggested that the two terminal oxo donors in SO are electronically equivalent. However, the consensus structure of the catalytically competent Mo(VI) active site in SO is five-coordinate square pyramidal, possessing two terminal oxo donors, an ene-1,2-dithiolate chelate and a cysteine sulfur donor ligand. Computational studies at the density functional level of theory have been performed on a minimal model of the SO active site, [Mo(VI)O2(S2C2Me2)(SCH3)]-, inC1symmetry to evaluate the composition of the LUMO, which is the putative electron acceptor orbital in the oxygen atom transfer (OAT) reaction with the sulfite substrate. The LUMO in this model is principally composed of a Mo dxy− pπ* interaction between the Mo and the equatorial oxygen (Oeq), while the axial oxygen (Oax) possesses no contribution to this orbital. In fact, the LUMO+1 orbital which possesses a substantial amount of Oaxcharacter lies nearly 1 eV higher in energy than the LUMO. It has also been suggested that changes in the Oax−Mo−Sthiolate−C torsion angle during the course of enzyme catalysis may aid in selection of Oeqfor OAT. Calculations were performed in which this torsion angle was varied by 20° through 360°. These calculations demonstrate that the Mo dxy−Oeqpπ* interaction, and therefore the Oeqatom character, always dominates the LUMO. The results presented here suggest that oxygen atom selection and activation are a direct function of the low-symmetry structure of the oxidized SO active site and provide a role for the ene-1,2-dithiolate in promoting OAT reactivity through its kinetic trans effect on the equatorial oxo donor.