Crystallographic Snapshots of the Zika Virus NS3 Helicase Help Visualize the Reactant Water Replenishment

Zika virus (ZIKV), a positive-strand
RNA virus belonging to the Flavivirus genus, has
become an urgent public health concern since recent outbreaks worldwide.
Its genome replication is facilitated by the viral NS3 protein bearing
helicase function. The NS3 helicase uses energy derived from adenosine
triphosphate (ATP) hydrolysis to unwind RNA duplexed regions. Structural
studies of the flavivirus NS3 helicases have suggested a conserved
mechanism of ATP hydrolysis. However, the process of the reactant
water replenishment, a key part of the hydrolysis cycle, remains elusive.
Here, we report two high-resolution crystal structures of ZIKV NS3
helicase in complex with adenosine diphosphate (ADP) and Mn2+, one with the reactant water already loaded as previously observed
and the other with the water molecule still in a loading state. These
data suggest that the reactant water replenishment can occur between
the release of phosphate and the release of ADP and improves the structural
basis of the NS3 ATP hydrolysis cycle.