Thiabendazole inhibits ubiquinone reduction activity of mitochondrial respiratory complex II via a water molecule mediated binding feature
Thiabendazole inhibits ubiquinone reduction activity of mitochondrial respiratory complex II via a water molecule mediated binding feature
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DOI：
10.1007/s13238-011-1079-1
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发表时间：
2011-07-01
期刊：
影响因子：
21.1
通讯作者：
Sun, Fei
中科院分区：
文献类型：
--
作者：
Zhou, Qiangjun;Zhai, Yujia;Sun, Fei
线粒体呼吸复合体II或琥珀酸：泛醌氧化还原酶(SQR)是三元酸循环和有氧呼吸中的关键膜复合体。用酶法和结晶学方法研究了5种消毒剂化合物对猪线粒体SQR泛醌还原活性的抑制作用。与噻苯咪唑(TBZ)结合的SQR的晶体结构在水分子起重要作用的泛醌结合部位显示了不同的缓蚀剂结合特征。基于生化数据的明显的抑制作用(IC50类似于100MU/L)和显著的基于结构的结合亲和力计算(类似于94MU/L)，使人怀疑其作为一种良好的消毒剂化合物用于线虫感染治疗和水果贮藏。
The mitochondrial respiratory complex II or succinate: ubiquinone oxidoreductase (SQR) is a key membrane complex in both the tricarboxylic acid cycle and aerobic respiration. Five disinfectant compounds were investigated with their potent inhibition effects on the ubiquinone reduction activity of the porcine mitochondrial SQR by enzymatic assay and crystallography. Crystal structure of the SQR bound with thiabendazole (TBZ) reveals a different inhibitor-binding feature at the ubiquinone binding site where a water molecule plays an important role. The obvious inhibitory effect of TBZ based on the biochemical data (IC50 similar to 100 mu mol/L) and the significant structure-based binding affinity calculation (similar to 94 mu mol/L) draw the suspicion of using TBZ as a good disinfectant compound for nematode infections treatment and fruit storage.