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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 C? atom of the methionine portion of the molecules that occupy the RNA binding tunnel may provide better specificity relative to human RNA methyltransferases.

SUBMITTER: Coloma J

PROVIDER: S-EPMC5074680 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Structures of NS5 Methyltransferase from Zika Virus.

Coloma Javier J Jain Rinku R Rajashankar Kanagalaghatta R KR García-Sastre Adolfo A Aggarwal Aneel K AK

Cell reports 20160912 12

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 ...[more]

PMID: 27633330

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