Crystal structure of full‐length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5

• Published in: Acta crystallographica. Section F, Structural biology communications Structural biology communications, 2017-03, Vol.73 (3), p.116-122
• Main Authors: Upadhyay, Anup K., Cyr, Matthew, Longenecker, Kenton, Tripathi, Rakesh, Sun, Chaohong, Kempf, Dale J.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Amino Acid Motifs; Binding Sites; Cations, Divalent; Cloning, Molecular; Crystal structure; Crystallography, X-Ray; Drugs; Encephalitis; Encephalitis Virus, Japanese - chemistry; Encephalitis Virus, Japanese - metabolism; Epidemics; Escherichia coli - genetics; Escherichia coli - metabolism; Flaviviridae; Gene Expression; Health hazards; Models, Molecular; nonstructural protein 5; NS5; Plasmids - chemistry; Plasmids - metabolism; Polymerase; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Proteins; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Research Communications; Ribonucleic acids; Structural Homology, Protein; Vector-borne diseases; Viral Nonstructural Proteins - chemistry; Viral Nonstructural Proteins - genetics; Viral Nonstructural Proteins - metabolism; Viruses; Zika virus; Zika Virus - chemistry; Zika Virus - metabolism; Zinc - chemistry; Zinc - metabolism
• ISSN: 2053-230X; 2053-230X
• DOI: 10.1107/S2053230X17001601

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. The recent epidemic of Zika virus (ZIKV) has created a major global health concern. Here, the crystal structure of the full‐length ZIKV NS5 protein at 3.05 Å resolution is presented to facilitate the structure‐based design of antiviral agents against ZIKV.