Mechanistic insight into the nitrosylation of the [4Fe-4S] cluster of WhiB-like proteins.
Mechanistic insight into the nitrosylation of the [4Fe-4S] cluster of WhiB-like proteins.
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DOI：
10.1021/ja109581t
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发表时间：
2011-02-02
影响因子：
15
通讯作者：
Le Brun NE
中科院分区：
文献类型：
--
作者：
Crack JC;Smith LJ;Stapleton MR;Peck J;Watmough NJ;Buttner MJ;Buxton RS;Green J;Oganesyan VS;Thomson AJ;Le Brun NE
蛋白质结合的铁硫簇与一氧化氮 (NO) 的反应性已有详细记录，但人们对簇亚硝基化的实际机制知之甚少。在这里，我们报告了对含有 [4Fe−4S] 的 Wbl 家族成员的研究，这些蛋白质在调节放线菌（包括链霉菌和分枝杆菌）的发育过程中发挥着关键作用，并且已被证明具有 NO 响应性。天蓝色链霉菌 WhiD 和结核分枝杆菌 WhiB1 在多相反应中与 NO 发生极快的反应，值得注意的是，每个 [4Fe−4S] 簇有 8 个 NO 分子。该反应比用 O2 观察到的反应快 104 倍，是迄今为止报道的最快的铁硫簇亚硝基化反应。通过测定硫产物及其氧化态，建立了 [Fe4S4(Cys)4]2− + 8NO → 2[FeI2(NO)4(Cys)2]0 + S2− + 3S0 的总体化学计量。动力学分析得出了一个四步机制，可以解释观察到的 NO 依赖性。 DFT 计算表明亚硝基化产物可能是由一对 Roussin 红酯 (RRE) 复合物二聚化而衍生的新型簇 [FeI4(NO)8(Cys)4]0。
The reactivity of protein bound iron−sulfur clusters with nitric oxide (NO) is well documented, but little is known about the actual mechanism of cluster nitrosylation. Here, we report studies of members of the Wbl family of [4Fe−4S] containing proteins, which play key roles in regulating developmental processes in actinomycetes, including Streptomyces and Mycobacteria, and have been shown to be NO responsive. Streptomyces coelicolor WhiD and Mycobacterium tuberculosis WhiB1 react extremely rapidly with NO in a multiphasic reaction involving, remarkably, 8 NO molecules per [4Fe−4S] cluster. The reaction is 104-fold faster than that observed with O2 and is by far the most rapid iron−sulfur cluster nitrosylation reaction reported to date. An overall stoichiometry of [Fe4S4(Cys)4]2− + 8NO → 2[FeI2(NO)4(Cys)2]0 + S2− + 3S0 has been established by determination of the sulfur products and their oxidation states. Kinetic analysis leads to a four-step mechanism that accounts for the observed NO dependence. DFT calculations suggest the possibility that the nitrosylation product is a novel cluster [FeI4(NO)8(Cys)4]0 derived by dimerization of a pair of Roussin’s red ester (RRE) complexes.
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影响因子：
4.4
作者：
HAY, PJ;WADT, WR
通讯作者：
WADT, WR
影响因子：
3.2
作者：
Daniel, J;Deb, C;Kolattukudy, PE
通讯作者：
Kolattukudy, PE
影响因子：
4.8
作者：
Jakimowicz, P;Cheesman, MR;Buttner, MJ
通讯作者：
Buttner, MJ
影响因子：
4.4
作者：
BECKE, AD
通讯作者：
BECKE, AD
影响因子：
3.9
作者：
Gergel, D;Cederbaum, AI
通讯作者：
Cederbaum, AI