title: The conformational changes of Zika virus methyltransferase upon converting SAM to SAH.
abstract: An outbreak of Zika virus (ZIKV) infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly potentially associated with ZIKV infection has already caused a public health emergency of international concern. Currently, there are no clinically effective vaccines or antiviral drugs available to treat ZIKV infection. The methyltransferase domain (MTase) of ZIKV nonstructural protein 5 (NS5) can sequentially methylate guanine N-7 and ribose 2'-O to form m7NGpppA2'Om cap structure in the new RNA transcripts. This methylation step is crucial for ZIKV replication cycle and evading the host immune system, making it a target for drug design. Here, we present the 1.76 Å crystal structure of ZIKV MTase in complex with the byproduct SAH, providing insight into the elegant methylation process, which will benefit the following antiviral drug development.
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China.|Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin 300457, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhou
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China.
authors.forename: Haofeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China.
authors.forename: Deping
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China.
authors.forename: Zefang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lanfeng
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tianjin University, Tianjin 300072, China.|Tianjin International Joint Academy of Biotechnology and Medicine, Tianjin 300457, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Yang
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006801:Humans; D008780:Methyltransferases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D012435:S-Adenosylhomocysteine / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism; D000071244:Zika Virus / Q000201:enzymology*
chemical_list: D017361:Viral Nonstructural Proteins; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008780:Methyltransferases
keywords: SAH; Zika virus; antiviral drug development; crystal structure; methyltransferase