Binding of histidine in the (Cys)3(His)1-coordinated [2Fe-2S] cluster of human mitoNEET.
Binding of histidine in the (Cys)3(His)1-coordinated [2Fe-2S] cluster of human mitoNEET.
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DOI：
10.1021/ja909359g
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发表时间：
2010-02-17
影响因子：
15
通讯作者：
Stoll, Stefan
中科院分区：
文献类型：
--
作者：
Dicus, Michelle M.;Conlan, Andrea;Nechushtai, Rachel;Jennings, Patricia A.;Paddock, Mark L.;Britt, R. David;Stoll, Stefan
人mitoNEET是一种位于线粒体外膜的同型二聚体铁硫蛋白，功能未知，但已知与噻唑烷二酮糖尿病药物相互作用。每个单体容纳具有不寻常的（Cys）3（His）1连接的[2Fe-2S]簇。His配体对于实现簇释放和调节氧化还原电位是重要的。我们使用多频（X-，Ka-，Q-波段）和多技术（CW，ESEEM，ENDOR，HYSCORE）EPR谱研究了团簇的顺磁还原态[Fe ~（2+）Fe ~（3+）]（S = 1/2）。它具有菱形g张量（2.007，1.937，1.897），平均g值为1.947，福尔斯介于Rieske型和铁氧还蛋白型[2Fe-2S]团簇之间。对14 N和15 N标记的mitoNEET的取向选择性Ka和Q带ENDOR、1D ESEEM和HYSCORE光谱进行模拟和最小二乘拟合，得到了连接组氨酸氮Nδ的超精细张量（14 N：Aiso = −6.25 MHz，T = −0.94 MHz）和四极张量（e2 Qq/h = −2.47 MHz，η = +0.38）的主值和取向。从这些，我们可以推断出g张量相对于团簇的绝对取向：g2轴接近垂直于[2Fe-2S]平面，g1和g2在平面内，但从Fe-Fe和S-S轴倾斜。在X-带ENDOR和ESEEM光谱中，可以看到弱耦合的氮，最有可能是质子化状态下组氨酸的Nε。我们发现，该集团是在一个价局域化的状态，其中Fe 2+是His结合。的场扫描光谱显示簇间偶极耦合的证据，可以使用一个未耦合的自旋模型为每个集群（SFe 2 + = 2，SFe 3 + = 5/2）进行模拟。在这项工作中确定的参数可以作为报告的集群结构是如何改变pH值的变化和药物结合。
Human mitoNEET is a homodimeric iron-sulfur protein located in the outer mitochondrial membrane with unknown function, but which is known to interact with thiazolidinedione diabetes drugs. Each monomer houses a [2Fe-2S] cluster with an unusual (Cys)3(His)1 ligation. The His ligand is important for enabling cluster release and for tuning the redox potential. We use multi-frequency (X-, Ka-, Q-band) and multi-technique (CW, ESEEM, ENDOR, HYSCORE) EPR spectroscopy to investigate the cluster in its paramagnetic reduced [Fe2+Fe3+] (S = 1/2) state. It has a rhombic g-tensor (2.007, 1.937, 1.897) with an average g-value of 1.947 that falls between those of Rieske-type and ferredoxin-type [2Fe-2S] clusters. Simulation and least-squares fitting of orientation-selective Ka- and Q-band ENDOR, 1D ESEEM and HYSCORE spectra of 14N and 15N-labelled mitoNEET yield the principal values and orientations of both the hyperfine tensor (14N: Aiso = −6.25 MHz, T = −0.94 MHz) and the quadrupolar tensor (e2Qq/h = −2.47 MHz, η = +0.38) of the ligating histidine nitrogen Nδ. From these, we can infer the absolute g tensor orientation with respect to the cluster: The g2 axis is close to perpendicular to the [2Fe-2S] plane, and g1 and g2 are in-plane, but skewed from the Fe-Fe and S-S axes. In X-band ENDOR and ESEEM spectra, a weakly coupled nitrogen is visible, most likely the Nε of the histidine in the protonated state. We find that the cluster is in a valence-localized state, where Fe2+ is His-bound. The field-sweep spectra show evidence of inter-cluster dipolar coupling that can be simulated using an uncoupled spin model for each cluster (SFe2+ = 2, SFe3+ = 5/2). The parameters determined in this work can function as reporters on how the cluster structure is altered upon pH changes and drug binding.
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影响因子：
5.6
作者：
Conlan, Andrea R.;Axelrod, Herbert L.;Paddock, Mark L.
通讯作者：
Paddock, Mark L.
影响因子：
15
作者：
Dikanov, SA;Xun, LY;Bowman, MK
通讯作者：
Bowman, MK
DOI：
10.1016/0005-2795(79)90091-6
发表时间：
1979-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
BERTRAND, P;GAYDA, JP
通讯作者：
GAYDA, JP
影响因子：
15
作者：
ASHBY, CIH;CHENG, CP;BROWN, TL
通讯作者：
BROWN, TL
影响因子：
2.9
作者：
Bowman, MK;Berry, EA;Kramer, DM
通讯作者：
Kramer, DM