Facile and dynamic cleavage of every iron-sulfide bond in cuboidal iron-sulfur clusters.
Facile and dynamic cleavage of every iron-sulfide bond in cuboidal iron-sulfur clusters.
复制标题
DOI：
10.1073/pnas.2210528120
复制
发表时间：
2023-02-07
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
铁硫簇蛋白存在于所有生命王国中，并执行不同的细胞功能。越来越多的结构生物学证据表明，它们的反应性可能是通过它们的簇核心的重排来实现的。在这里，我们表明，铁离子的特权，立方体集群快速交换与外源Fe 2+离子，因此比通常赞赏的动态。这种现象在一系列的集群中得到了证实，并发展成为一种简单的方法，用于生物成因的Fe-S集群的同位素富集。这种方法的应用将有助于光谱和机械分析这类无处不在的金属蛋白。自然界利用弱场簇来支持广泛的生物过程。最普遍的团簇是立方体的Fe-S团簇，它由具有局部高自旋电子构型的Fe位组成。这种配置提高了配体交换的速率，并使簇具有一定程度的结构可塑性，这种可塑性越来越被认为与功能相关。在这里，我们使用同位素示踪实验来研究这种现象。具体来说，我们证明了合成[Fe 4S 4]和[MoFe 3S 4]簇交换它们的Fe原子与溶解在溶液中的Fe 2+离子，一个过程，涉及可逆的分裂和重整的每个Fe-S键在簇核心。这种交换是容易的，在大多数情况下发生在室温下的时间尺度上的分钟，并记录在一系列的集群核心氧化态和终端连接模式。除了提出一个高度动态的集群结构的图片，这些结果提供了一种方法，用于同位素标记预形成的集群与自旋活性核，如57 Fe。这样的协议被证明为自由基S-腺苷-L-甲硫氨酸酶，RlmN。
Iron–sulfur cluster proteins are found in all kingdoms of life and perform diverse cellular functions. Increasingly, evidence from structural biology suggests that their reactivity may be enabled by rearrangements of their cluster cores. We show here that the Fe ions in thermodynamically privileged, cuboidal clusters rapidly exchange with exogenous Fe2+ ions, and are thus more dynamic than commonly appreciated. This phenomenon is demonstrated across a range of clusters and is developed into a straightforward method for isotopic enrichment of biogenic Fe–S clusters. Applications of this method will facilitate spectroscopic and mechanistic analysis of this ubiquitous class of metalloproteins. Nature employs weak-field metalloclusters to support a wide range of biological processes. The most ubiquitous metalloclusters are the cuboidal Fe–S clusters, which are comprised of Fe sites with locally high-spin electronic configurations. Such configurations enhance rates of ligand exchange and imbue the clusters with a degree of structural plasticity that is increasingly thought to be functionally relevant. Here, we examine this phenomenon using isotope tracing experiments. Specifically, we demonstrate that synthetic [Fe4S4] and [MoFe3S4] clusters exchange their Fe atoms with Fe2+ ions dissolved in solution, a process that involves the reversible cleavage and reformation of every Fe–S bond in the cluster core. This exchange is facile—in most cases occurring at room temperature on the timescale of minutes—and documented over a range of cluster core oxidation states and terminal ligation patterns. In addition to suggesting a highly dynamic picture of cluster structure, these results provide a method for isotopically labeling pre-formed clusters with spin-active nuclei, such as 57Fe. Such a protocol is demonstrated for the radical S-adenosyl-l-methionine enzyme, RlmN.
登录
查看更多内容
影响因子：
15
作者：
HAGEN, KS;REYNOLDS, JG;HOLM, RH
通讯作者：
HOLM, RH
影响因子：
2.3
作者：
Komuro, Takashi;Kawaguchi, Hiroyuki;Tatsumi, Kazuyuki
通讯作者：
Tatsumi, Kazuyuki
自由基 SAM 酶进行甲基转移的结构基础。
DOI：
10.1126/science.1205358
发表时间：
2011-05-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Boal AK;Grove TL;McLaughlin MI;Yennawar NH;Booker SJ;Rosenzweig AC
通讯作者：
Rosenzweig AC
影响因子：
4.6
作者：
Brown, Alexandra C.;Suess, Daniel L. M.
通讯作者：
Suess, Daniel L. M.
影响因子：
4.6
作者：
Benediktsson, Bardi;Bjornsson, Ragnar
通讯作者：
Bjornsson, Ragnar