中国科学技术大学生命科学学院金腾川课题组利用X晶体衍射技术，首次清晰捕捉到寨卡病毒解旋酶只结合三磷酸核苷（NTP）、与NTP-金属离子结合后的激活初始态及NTP水解后的状态，成功揭示了金属离子激活寨卡病毒NS3解旋酶的分子机制。研究成果以“Molecular Mechanism of Divalent-Metal-Induced Activation of NS3 Helicase and Insights into Zika Virus Inhibitor Design”为题，于10月19日在线发表于《Nucleic Acids Research》杂志。
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 structuralevidence on the allosteric modulation of MgNTP2- on the NS3 helicase activity. Furthermore, the compact conformation of inhibitory NTP identified in this study provides precise information for the rational drug design of small molecule inhibitors for the treatment of ZIKV infection.