Dong Geng, Ryde Ulf
Department of Theoretical Chemistry, Lund University, Chemical Centre , P.O. Box 124, SE-221 00 Lund, Sweden.
Inorg Chem. 2016 Nov 21;55(22):11727-11735. doi: 10.1021/acs.inorgchem.6b01732. Epub 2016 Nov 1.
Nonheme iron enzymes play an important role in the aerobic degradation of aromatic ring systems. Most enzymes can only cleave substrates with electron-rich substituents, e.g., with two hydroxyl groups. However, salicylate 1,2-dioxygenase (SDO) can cleave rings with only a single hydroxyl group. We investigated the oxygen-activation mechanism of the ring fission of salicylate by SDO by computational methods using combined quantum mechanical and molecular mechanical (QM/MM) geometry optimizations, large QM calculations with 493 atoms, and QM/MM free-energy perturbations. Our results demonstrate that the reactive Fe-O species is best described as a Fe(III)-O state, which is triplet O binding to quintet Fe(II), leading to a one-electron transfer from Fe(II) to O. Subsequently, the O group of this species attacks the aromatic ring of substrate to form an alkylperoxo intermediate. Mutation studies suggested that His162 is essential for catalysis. Our calculations indicate that His162 plays a role as an acid-base catalyst, providing a proton to the substrate.
非血红素铁酶在芳香环系统的有氧降解中发挥着重要作用。大多数酶只能切割带有富电子取代基的底物，例如带有两个羟基的底物。然而，水杨酸1,2 -双加氧酶（SDO）能够切割仅带有单个羟基的环。我们通过计算方法，采用量子力学和分子力学相结合（QM/MM）的几何优化、含493个原子的大型QM计算以及QM/MM自由能扰动，研究了SDO催化水杨酸环裂变的氧激活机制。我们的结果表明，反应性铁 - 氧物种最好描述为Fe(III)-O状态，即三线态的氧与五重态的Fe(II)结合，导致一个电子从Fe(II)转移到O。随后，该物种的O基团攻击底物的芳香环形成烷基过氧中间体。突变研究表明，His162对催化作用至关重要。我们的计算表明，His162作为酸碱催化剂发挥作用，为底物提供一个质子。
