- 作者: Shin-Ru Shih; Chiayn Chiang; Tzu-Chun Chen; Cheng-Nan Wu; John Tsu-An Hsu; Jin-Ching Lee; Ming-Jing Hwang; Mei-Ling Li; Guang-Wu Chen; Mei-Shan Ho
- 作者服務機構: School of Medical Technology, Chang Gung University, Clincal Virology Laboratory, Department of Clinical Pathology, Chang Gung Memorial Hospital,Tao-Yuan; Division of Biomedical Sciences, Academia Sinica, and Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Taipei; Department of Chemical Engineering, National Tsing Hua University, Division of Biostatistics and Bioinformatice, National Health Research Institutes, Taipei, Ttaiwan
- 中文摘要: --
- 英文摘要: The 3C protease (3CPr0) of enterovirus 71(EV71)is a goodmolecular target for drug discovery. Notably, this pro-tease was found to possess RNA-binding activity. Theregions responsible for RNA binding were classified as'KFRDI'(positions 82-86) and 'VGK'(positions 154-156)in 3CPr0 by mutagenesis study. Although the RNA-bind-ing regions are structurally distinct from the catalytic siteof EV71 3CPr0, mutations in the RNA-binding regionsinfluenced 3CPr0 proteolytic activity. In contrast, muta-tions at the catalytic site had almost no influence on RNAbinding ability. We identified certain mutations within3CPr0 which abrogated both the RNA-binding activity ofthe expressed, recombinant, protease and the ability torescue virus from an infectious full-length clone of EV71(pEV71). Interestingly, mutation at position 84 fromArg(R)to Lys(K) was found to retain good RNA bindingand proteolytic activity for the recombinant 3CPr0; how-ever, no virus could be rescued when pEV71 with theR84K mutation was introduced into the infectious copy.Together, these results may provide useful informationfor using 3CPr0 as the molecular target to develop anti-EV71 agents.
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