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Architecture of the mycobacterial succinate dehydrogenase with a membrane-embedded Rieske FeS cluster [Biochemistry]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.412 ) Pub Date : 2021-04-13 , DOI: 10.1073/pnas.2022308118
Xiaoting Zhou, Yan Gao, Weiwei Wang, Xiaolin Yang, Xiuna Yang, Fengjiang Liu, Yanting Tang, Sin Man Lam, Guanghou Shui, Lu Yu, Changlin Tian, Luke W. Guddat, Quan Wang, Zihe Rao, Hongri Gong

Complex II, also known as succinate dehydrogenase (SQR) or fumarate reductase (QFR), is an enzyme involved in both the Krebs cycle and oxidative phosphorylation. Mycobacterial Sdh1 has recently been identified as a new class of respiratory complex II (type F) but with an unknown electron transfer mechanism. Here, using cryoelectron microscopy, we have determined the structure of Mycobacterium smegmatis Sdh1 in the presence and absence of the substrate, ubiquinone-1, at 2.53-Å and 2.88-Å resolution, respectively. Sdh1 comprises three subunits, two that are water soluble, SdhA and SdhB, and one that is membrane spanning, SdhC. Within these subunits we identified a quinone-binding site and a rarely observed Rieske-type [2Fe-2S] cluster, the latter being embedded in the transmembrane region. A mutant, where two His ligands of the Rieske-type [2Fe-2S] were changed to alanine, abolished the quinone reduction activity of the Sdh1. Our structures allow the proposal of an electron transfer pathway that connects the substrate-binding and quinone-binding sites. Given the unique features of Sdh1 and its essential role in Mycobacteria, these structures will facilitate antituberculosis drug discovery efforts that specifically target this complex.



中文翻译:

带有膜包埋的Rieske FeS簇的分枝杆菌琥珀酸脱氢酶的结构[生物化学]

复合物II,也称为琥珀酸脱氢酶(SQR)或富马酸酯还原酶(QFR),是一种与克雷布斯循环和氧化磷酸化有关的酶。分枝杆菌Sdh1最近被鉴定为一类新型的呼吸道复合物II(F型),但其电子传递机制未知。在这里,我们使用冷冻电子显微镜确定了耻垢分枝杆菌的结构在存在和不存在底物泛醌-1的情况下,Sdh1的分辨率分别为2.53-Å和2.88-Å。Sdh1包含三个亚基,两个为水溶性SdhA和SdhB,另一个为跨膜SdhC。在这些亚基中,我们确定了一个醌结合位点和一个很少观察到的Rieske型[2Fe-2S]簇,后者嵌入跨膜区。一个突变体,其中两个Rieske型[2Fe-2S]的His配体变为丙氨酸,废除了Sdh1的醌还原活性。我们的结构允许提议一种将底物结合位点和醌结合位点连接起来的电子转移途径。鉴于Sdh1的独特功能及其在分枝杆菌中的重要作用,这些结构将有助于针对这种复合物的抗结核药物发现工作。

更新日期:2021-04-06
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