Structures of Enterovirus 71 3C proteinase (strain E2004104-TW-CDC) and its complex with rupintrivir

作者：Caiming Wu, Qixu Cai, Chen Chen, Ning Li, Xuanjia Peng, Yaxian Cai, Ke Yin, Xinsheng Chen, Xiaolong Wang, Rongfu Zhang, Lijie Liu, Shu‐Hui Chen, Jian Li, Tianwei Lin · 发表于：Acta Crystallographica Section D Biological Crystallography · 年份：2013 · DOI：10.1107/s0907444913002862 · 被引用次数：19 · 研究领域：Viral Infections and Immunology Research、RNA and protein synthesis mechanisms、Virus-based gene therapy research

The crystal structure of 3C proteinase (3C(pro)) from Enterovirus 71 (EV71) was determined in space group C2221 to 2.2 Å resolution. The fold was similar to that of 3C(pro) from other picornaviruses, but the difference in the β-ribbon reported in a previous structure was not observed. This β-ribbon was folded over the substrate-binding cleft and constituted part of the essential binding sites for interaction with the substrate. The structure of its complex with rupintrivir (AG7088), a peptidomimetic inhibitor, was also characterized in space group P212121 to 1.96 Å resolution. The inhibitor was accommodated without any spatial hindrance despite the more constricted binding site; this was confirmed by functional assays, in which the inhibitor showed comparable potency towards EV71 3C(pro) and human rhinovirus 3C(pro), which is the target that rupintrivir was designed against.