机构：[a]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,四川大学华西医院[b]Laboratory of Structural Biology and MOE Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing 100084, People’s Republic of China[c]National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, People’s Republic of China.
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 Mn2+-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 Mn2+ 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.
基金：
This work was supported by the National Natural Science
Foundation of China (Grant Nos. 31000332, 31100208,
31100877, 31170782 and 31110103915).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|4 区生物
小类|4 区生化研究方法4 区生化与分子生物学4 区生物物理4 区晶体学
最新[2023]版：
大类|4 区生物学
小类|4 区生化研究方法4 区生化与分子生物学4 区生物物理4 区晶体学
第一作者：
第一作者机构：[a]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,[b]Laboratory of Structural Biology and MOE Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing 100084, People’s Republic of China
共同第一作者：
通讯作者：
通讯机构：[a]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,[b]Laboratory of Structural Biology and MOE Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing 100084, People’s Republic of China
推荐引用方式(GB/T 7714)：
Lei Li,Jin Wang,Zhihui Jia,et al.Structural view of the helicase reveals that Zika virus uses a conserved mechanism for unwinding RNA.[J].Acta crystallographica. Section F, Structural biology communications.2018,74(Pt 4):205-213.doi:10.1107/S2053230X18003813.
APA：
Lei Li,Jin Wang,Zhihui Jia&Neil Shaw.(2018).Structural view of the helicase reveals that Zika virus uses a conserved mechanism for unwinding RNA..Acta crystallographica. Section F, Structural biology communications,74,(Pt 4)
MLA：
Lei Li,et al."Structural view of the helicase reveals that Zika virus uses a conserved mechanism for unwinding RNA.".Acta crystallographica. Section F, Structural biology communications 74..Pt 4(2018):205-213
