Binding of Reactive Oxygen Species at Fe-S Cubane Clusters
Binding of Reactive Oxygen Species at Fe-S Cubane Clusters
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DOI：
10.1002/chem.201503008
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发表时间：
2015-12-21
影响因子：
4.3
通讯作者：
Reiher, Markus
中科院分区：
文献类型：
--
作者：
Bruska, Marta K.;Stiebritz, Martin T.;Reiher, Markus
活性氧 (ROS) 在细胞的生物化学中发挥着重要作用，并发生在退行性过程和信号转导中。铁硫蛋白对氧特别敏感，其无机辅助因子经常发生 ROS 诱导的分解反应。由于有关这些过程的实验知识仍然不完整，我们在此提出了最相关的 ROS 与 [Fe4S4] 簇结合的相对能量学的量子化学研究。我们发现，具有一个不配位 Fe 原子的立方烷簇（例如在乌头酸酶中发现的）与所有考虑的氧衍生物结合，而三线态 O-2 活化为单线态 O-2 是与这些簇中价饱和铁中心结合所必需的。 NO 和 OH 基团与 Fe 原子具有最强的放热结合能。配位半胱氨酸残基的直接磺化氧化只能通过 OH 或 H2O2 作为攻击剂。这里建立的 ROS 与铁硫簇结合的热力学图可以作为研究簇嵌入蛋白环境对 ROS 诱导的铁硫蛋白分解的反应调节作用的起点。
Reactive oxygen species (ROS) play an important role in the biochemistry of the cell and occur in degenerative processes as well as in signal transduction. Iron-sulfur proteins are particularly oxygen-sensitive and their inorganic cofactors frequently undergo ROS-induced decomposition reactions. As experimental knowledge about these processes is still incomplete we present here a quantum chemical study of the relative energetics for the binding of the most relevant ROS to [Fe4S4] clusters. We find that cubane clusters with one uncoordinated Fe atom (as found, for instance, in aconitase) bind all oxygen derivatives considered, whereas activation of triplet O-2 to singlet O-2 is required for binding to valence-saturated iron centers in these clusters. The radicals NO and OH feature the most exothermic binding energies to Fe atoms. Direct sulfoxidation of coordinating cysteine residues is only possible by OH or H2O2 as attacking agents. The thermodynamic picture of ROS binding to iron-sulfur clusters established here can serve as a starting point for studying reactivity-modulating effects of the cluster-embedding protein environment on ROS-induced decomposition of iron-sulfur proteins.