title: Structures of NS5 Methyltransferase from Zika Virus.
abstract: The Zika virus (ZIKV) poses a major public health emergency. To aid in the development of antivirals, we present two high-resolution crystal structures of the ZIKV NS5 methyltransferase: one bound to S-adenosylmethionine (SAM) and the other bound to SAM and 7-methyl guanosine diphosphate (7-MeGpp). We identify features of ZIKV NS5 methyltransferase that lend to structure-based antiviral drug discovery. Specifically, SAM analogs with functionalities on the Cβ atom of the methionine portion of the molecules that occupy the RNA binding tunnel may provide better specificity relative to human RNA methyltransferases.
authors.affiliation: Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Coloma
authors.affiliation: Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Rinku
authors.initials: R
authors.lastname: Jain
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA; NE-CAT, Advanced Photon Source, Argonne, IL 60439, USA.
authors.forename: Kanagalaghatta R
authors.initials: KR
authors.lastname: Rajashankar
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: aneel.aggarwal@mssm.edu.
authors.forename: Aneel K
authors.initials: AK
authors.lastname: Aggarwal
mesh_terms: D008780:Methyltransferases / Q000737:chemistry*; D011487:Protein Conformation; D017361:Viral Nonstructural Proteins / Q000737:chemistry*; D000071244:Zika Virus / Q000737:chemistry* / Q000201:enzymology*
chemical_list: D017361:Viral Nonstructural Proteins; D008780:Methyltransferases