噻苯达唑通过水分子介导的结合特征抑制线粒体呼吸复合物 II 的泛醌还原活性。
Thiabendazole inhibits ubiquinone reduction activity of mitochondrial respiratory complex II via a water molecule mediated binding feature.
机构信息
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
出版信息
Protein Cell. 2011 Jul;2(7):531-42. doi: 10.1007/s13238-011-1079-1. Epub 2011 Aug 6.
Abstract
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 (IC(50) 100 μmol/L) and the significant structure-based binding affinity calculation (94 μmol/L) draw the suspicion of using TBZ as a good disinfectant compound for nematode infections treatment and fruit storage.
摘要
线粒体呼吸复合物 II 或琥珀酸：泛醌氧化还原酶（SQR）是三羧酸循环和需氧呼吸中关键的膜复合物。通过酶促测定和晶体学研究了五种消毒剂化合物对猪线粒体 SQR 中泛醌还原活性的强烈抑制作用。SQR 与噻苯达唑（TBZ）结合的晶体结构揭示了在泛醌结合位点存在不同的抑制剂结合特征，其中水分子起着重要作用。基于生化数据（IC50100 μmol/L）和显著的基于结构的结合亲和力计算（94 μmol/L）的 TBZ 的明显抑制作用，使人怀疑 TBZ 可用作线虫感染治疗和水果储存的良好消毒剂化合物。
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