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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.

SUBMITTER: Zhou H

PROVIDER: S-EPMC5362447 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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The conformational changes of Zika virus methyltransferase upon converting SAM to SAH.

Zhou Han H Wang Fenghua F Wang Haofeng H Chen Cheng C Zhang Tianqing T Han Xu X Wang Deping D Chen Chen C Wu Chen C Xie Wei W Wang Zefang Z Zhang Lei L Wang Lanfeng L Yang Haitao H

Oncotarget 20170201 9

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 ...[more]

PMID: 28122329

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Crystal structure and ligand-induced folding of the SAM/SAH riboswitch.

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