Structural basis for difunctional mechanism of m-AMSA against African swine fever virus pP1192R

文献类型： 外文期刊

第一作者： Liu, Ruili

作者： Liu, Ruili;Cheng, Yingxian;Liu, Ruili;Sun, Junqing;Li, Lian-Feng;Li, Meilin;Li, Su;Wang, Yanjin;Qiu, Hua-Ji;Cheng, Yingxian;Fu, Lifeng;Qu, Xiao;Qi, Jianxun;Gao, George Fu;Peng, Guorui;Liu, Sheng;Ran, Jiaqi;Li, Xiaomei;Pang, Erqi;Wang, Yanli;Wang, Han

作者机构：

期刊名称：NUCLEIC ACIDS RESEARCH （ 影响因子：16.6； 五年影响因子：16.1 ）

ISSN： 0305-1048

年卷期： 2024 年

页码：

收录情况： SCI

摘要： The African swine fever virus (ASFV) type II topoisomerase (Topo II), pP1192R, is the only known Topo II expressed by mammalian viruses and is essential for ASFV replication in the host cytoplasm. Herein, we report the structures of pP1192R in various enzymatic stages using both X-ray crystallography and single-particle cryo-electron microscopy. Our data structurally define the pP1192R-modulated DNA topology changes. By presenting the A(2+)-like metal ion at the pre-cleavage site, the pP1192R-DNA-m-AMSA complex structure provides support for the classical two-metal mechanism in Topo II-mediated DNA cleavage and a better explanation for nucleophile formation. The unique inhibitor selectivity of pP1192R and the difunctional mechanism of pP1192R inhibition by m-AMSA highlight the specificity of viral Topo II in the poison binding site. Altogether, this study provides the information applicable to the development of a pP1192R-targeting anti-ASFV strategy. [GRAPHICS] .

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