Li Lei, Wang Jin, Jia Zhihui, Shaw Neil
State Key Laboratory of Biotherapy and Cancer Center/National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Laboratory of Structural Biology and MOE Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing 100084, People's Republic of China.
Acta Crystallogr F Struct Biol Commun. 2018 Apr 1;74(Pt 4):205-213. doi: 10.1107/S2053230X18003813. Epub 2018 Mar 22.
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.
最近的研究表明，寨卡病毒（ZIKV）感染与神经并发症的发生之间存在联系。缺乏针对ZIKV的治疗方法已引起全球医疗专业人员的警觉。在此，报道了ZIKV必需解旋酶的无配体形式以及与AMPPNP和锰结合形式的晶体结构，其分辨率分别细化至1.78 Å和1.3 Å。这些结构揭示了解旋酶保守的三模块拓扑结构。ATP和锰通过保守的氢键相互作用连接在两个类RecA结构域之间。配体的结合会诱导主链Cα和侧链原子的移动。在AMPPNP附近观察到大量溶剂分子，表明其在催化中起作用。这些高分辨率结构可能有助于设计针对ZIKV解旋酶的抑制剂，以治疗由ZIKV引起的感染。
