Inhibitors of mitochondrial respiratory complex II
(In collaboration with Prof. Jizhong Lou, IBP)
1. Thiabendazole inhibits ubiquinone reduction activity of mitochondrial respiratory complex II via a new binding motif.
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 new inhibitor-binding motif at the ubiquinone binding site. Obvious inhibitory effect of TBZ from the biochemical data (IC50 ~ 100uM) and the significant structure-based binding affinity calculation (~94uM) draw the suspicion of using TBZ as a good disinfectant compound for nematode infections treatment and fruit storage.
Reference:
Zhou Q., Zhai Y., Lou J., Liu M., Pang X. and Sun F.* (2011), Thiabendazole inhibits ubiquinone reduction activity of mitochondrial respiratory complex II via a water molecule mediated binding feature. Protein & Cell, 2(7):531-542.
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