title: Structures of Enterovirus 71 3C proteinase (strain E2004104-TW-CDC) and its complex with rupintrivir.
abstract: 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.
authors: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, People's Republic of China.
authors: Caiming
authors: C
authors: Wu
authors: Qixu
authors: Q
authors: Cai
authors: Chen
authors: C
authors: Chen
authors: Ning
authors: N
authors: Li
authors: Xuanjia
authors: X
authors: Peng
authors: Yaxian
authors: Y
authors: Cai
authors: Ke
authors: K
authors: Yin
authors: Xinsheng
authors: X
authors: Chen
authors: Xiaolong
authors: X
authors: Wang
authors: Rongfu
authors: R
authors: Zhang
authors: Lijie
authors: L
authors: Liu
authors: Shuhui
authors: S
authors: Chen
authors: Jian
authors: J
authors: Li
authors: Tianwei
authors: T
authors: Lin
mesh_terms: D000086042:3C Viral Proteases; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D002460:Cell Line / Q000187:drug effects / Q000821:virology; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D029821:Enterovirus A, Human / Q000201:enzymology*; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000031:analogs & derivatives; D011487:Protein Conformation; D011760:Pyrrolidinones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D015853:Cysteine Proteinase Inhibitors; D007555:Isoxazoles; D011760:Pyrrolidinones; D014764:Viral Proteins; D010649:Phenylalanine; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; D014633:Valine; C118874:rupintrivir
keywords: 3C proteinases; EV71; Enterovirus; drug design; hand, foot and mouth disease; rupintrivir