Molecular mechanism of divalent-metal-induced activation of NS3 helicase and insights into Zika virus inhibitor design.

ABSTRACT: Zika virus has attracted increasing attention because of its potential for causing human neural disorders, including microcephaly in infants and Guillain-Barré syndrome. Its NS3 helicase domain plays critical roles in NTP-dependent RNA unwinding and translocation during viral replication. Our structural analysis revealed a pre-activation state of NS3 helicase in complex with GTPγS, in which the triphosphate adopts a compact conformation in the absence of any divalent metal ions. In contrast, in the presence of a divalent cation, GTPγS adopts an extended conformation, and the Walker A motif undergoes substantial conformational changes. Both features contribute to more extensive interactions between the GTPγS and the enzyme. Thus, this study provides structural evidence on the allosteric mod

SUBMITTER: Cao X 

PROVIDER: S-EPMC5137455 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature