title: The structure of Zika virus NS5 reveals a conserved domain conformation.
abstract: The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one of the two alternative conformations of flavivirus NS5 proteins. The activity of this NS5 protein is verified through a de novo RdRp assay on a subgenomic ZIKV RNA template. Importantly, our structural analysis leads to the identification of a potential drug-binding site of ZIKV NS5, which might facilitate the development of novel antivirals for ZIKV.
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, California 92521, USA.
authors.forename: Boxiao
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, California 92521, USA.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Tan
authors.affiliation: Department of Plant Pathology and Microbiology, University of California, Riverside, Riverside, California 92521, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Thurmond
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, California 92521, USA.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, California 92521, USA.
authors.forename: Asher
authors.initials: A
authors.lastname: Lin
authors.affiliation: Department of Plant Pathology and Microbiology, University of California, Riverside, Riverside, California 92521, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Hai
authors.affiliation: Department of Biochemistry, University of California, Riverside, Riverside, California 92521, USA.
authors.forename: Jikui
authors.initials: J
authors.lastname: Song
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D011487:Protein Conformation; D012367:RNA, Viral / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism; D013698:Templates, Genetic; D017361:Viral Nonstructural Proteins / Q000737:chemistry*; D000071244:Zika Virus / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics
chemical_list: D000998:Antiviral Agents; C096041:NS5 protein, flavivirus; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D012324:RNA-Dependent RNA Polymerase