Structural View of the Helicase Reveals That Zika Virus Uses a Conserved Mechanism for Unwinding RNA
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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-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 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.
Crystal structure of the NS3-like helicase from Alongshan virus.
Gao X, Zhu K, Wojdyla J, Chen P, Qin B, Li Z IUCrJ. 2020; 7(Pt 3):375-382.
PMID: 32431821 PMC: 7201283. DOI: 10.1107/S2052252520003632.