Crystal Structure Analysis of the Repair of Iron Centers Protein YtfE and Its Interaction with NO
Crystal Structure Analysis of the Repair of Iron Centers Protein YtfE and Its Interaction with NO
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DOI：
10.1002/chem.201600990
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发表时间：
2016-07-04
影响因子：
4.3
通讯作者：
Liaw, Wen-Feng
中科院分区：
文献类型：
--
作者：
Lo, Feng-Chun;Hsieh, Chang-Chih;Liaw, Wen-Feng
微生物蛋白YtfE修复亚硝基化[Fe-S]簇的分子机制仍然知之甚少。YtfE的X射线晶体结构，结合EPR，磁性圆二色性（MCD），UV和O-17标记的电子自旋回波包络调制测量，表明氧桥Fe-II-Fe-III二铁核心的每个铁是配位不饱和的，每个铁结合到两个桥接羧酸盐和两个末端组氨酸，除了氧桥。结构分析表明，有两个溶剂可访问的隧道，这两个都收敛到二铁中心，并为捕获基板的关键。还原型FeII-FeII YtfE对一氧化氮的反应性表明，N2 O生产的先决条件需要两个铁位点同时被亚硝基化。具体而言，在还原偶联产生N2 O之前，两个铁位点的亚硝基化是协同的。这一结果表明，除了任何修复的铁中心（RIC）的活动，YtfE作为一个NO捕获清除剂，以促进NO转化为N2 O低NO通量下，这之前亚硝化应激。
Molecular mechanisms underlying the repair of nitrosylated [Fe-S] clusters by the microbial protein YtfE remain poorly understood. The X-ray crystal structure of YtfE, in combination with EPR, magnetic circular dichroism (MCD), UV, and O-17-labeling electron spin echo envelope modulation measurements, show that each iron of the oxo-bridged Fe-II-Fe-III diiron core is coordinatively unsaturated with each iron bound to two bridging carboxylates and two terminal histidines in addition to an oxo-bridge. Structural analysis reveals that there are two solvent-accessible tunnels, both of which converge to the diiron center and are critical for capturing substrates. The reactivity of the reduced-form FeII-FeII YtfE toward nitric oxide demonstrates that the prerequisite for N2O production requires the two iron sites to be nitrosylated simultaneously. Specifically, the nitrosylation of the two iron sites prior to their reductive coupling to produce N2O is cooperative. This result suggests that, in addition to any repair of iron centers (RIC) activity, YtfE acts as an NO-trapping scavenger to promote the NO to N2O transformation under low NO flux, which precedes nitrosative stress.