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Structural view of the helicase reveals that Zika virus uses a conserved mechanism for unwinding RNA.

ABSTRACT: Recent studies suggest a link between infection by Zika virus (ZIKV) and the development of neurological complications. The lack of ZIKV-specific therapeutics has alarmed healthcare professionals worldwide. Here, crystal structures of apo and AMPPNP- and Mn2+-bound forms of the essential helicase of ZIKV refined to 1.78 and 1.3?Å resolution, respectively, are reported. The structures reveal a conserved trimodular topology of the helicase. ATP and Mn2+ are tethered between two RecA-like domains by conserved hydrogen-bonding interactions. The binding of ligands induces the movement of backbone C? and side-chain atoms. Numerous solvent molecules are observed in the vicinity of the AMPPNP, suggesting a role in catalysis. These high-resolution structures could be useful for the design of inhibitors targeting the helicase of ZIKV for the treatment of infections caused by ZIKV.

SUBMITTER: Li L

PROVIDER: S-EPMC5894106 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Structural view of the helicase reveals that Zika virus uses a conserved mechanism for unwinding RNA.

Li Lei L Wang Jin J Jia Zhihui Z Shaw Neil N

Acta crystallographica. Section F, Structural biology communications 20180322 Pt 4

Recent studies suggest a link between infection by Zika virus (ZIKV) and the development of neurological complications. The lack of ZIKV-specific therapeutics has alarmed healthcare professionals worldwide. Here, crystal structures of apo and AMPPNP- and Mn<sup>2+</sup>-bound forms of the essential helicase of ZIKV refined to 1.78 and 1.3 Å resolution, respectively, are reported. The structures reveal a conserved trimodular topology of the helicase. ATP and Mn<sup>2+</sup> are tethered between t ...[more]

PMID: 29633968

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