title: Crystal structure of full-length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5.
abstract: The rapid spread of the recent Zika virus (ZIKV) epidemic across various countries in the American continent poses a major health hazard for the unborn fetuses of pregnant women. To date, there is no effective medical intervention. The nonstructural protein 5 of Zika virus (ZIKV-NS5) is critical for ZIKV replication through the 5'-RNA capping and RNA polymerase activities present in its N-terminal methyltransferase (MTase) and C-terminal RNA-dependent RNA polymerase (RdRp) domains, respectively. The crystal structure of the full-length ZIKV-NS5 protein has been determined at 3.05 Å resolution from a crystal belonging to space group P21212 and containing two protein molecules in the asymmetric unit. The structure is similar to that reported for the NS5 protein from Japanese encephalitis virus and suggests opportunities for structure-based drug design targeting either its MTase or RdRp domain.
authors.affiliation: AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA.
authors.forename: Anup K
authors.initials: AK
authors.lastname: Upadhyay
authors.affiliation: AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Cyr
authors.affiliation: AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA.
authors.forename: Kenton
authors.initials: K
authors.lastname: Longenecker
authors.affiliation: AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Tripathi
authors.affiliation: AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA.
authors.forename: Chaohong
authors.initials: C
authors.lastname: Sun
authors.affiliation: AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA.
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Kempf
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D002413:Cations, Divalent; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004664:Encephalitis Virus, Japanese / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D008958:Models, Molecular; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D040681:Structural Homology, Protein; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000071244:Zika Virus / Q000737:chemistry* / Q000378:metabolism; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; C096041:NS5 protein, flavivirus; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins; D015032:Zinc
keywords: NS5; Zika virus; nonstructural protein 5