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

Acta Crystallographica. Section F, Structural Biology Communications
Lei LiNeil Shaw

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 Cα 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.

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Citations

Nov 16, 2018·Expert Opinion on Investigational Drugs·Yingshan Han, Thibault Mesplède

Related Concepts

Zika virus (organism)
Protein Domain
Striadyne
Mg-5'-Adenylylimidodiphosphate
Polymorphism, Crystallization
Manganese
Protein Conformation
RNA, Viral
Viral Nonstructural Proteins NS2
Homologous Sequences

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