Structure of the error-prone DNA ligase of African swine fever virus identifies critical active site residues
Structure of the error-prone DNA ligase of African swine fever virus identifies critical active site residues
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非洲猪瘟病毒易错DNA连接酶的结构识别出关键活性位点残基
DOI：
10.1038/s41467-019-08296-w
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发表时间：
2019-01-23
影响因子：
16.6
通讯作者：
Gan, Jianhua
中科院分区：
文献类型：
--
作者：
Chen, Yiqing;Liu, Hehua;Gan, Jianhua
非洲猪瘟病毒（ASFV）具有传染性，可引起猪的高度致命性疾病。ASFV DNA连接酶（AsfvLIG）是迄今为止发现的最易出错的连接酶之一，它在ASFV的DNA修复过程中催化DNA连接反应，并在病毒基因组的突变中起重要作用。在这里，我们报告了四个AsfvLIG：DNA复合物的结构，并证明AsfvLIG具有独特的N-末端结构域（NTD），在底物结合和催化复合物组装中起着关键作用。结合诱变、体外结合和催化测定，我们的研究揭示了四个独特的活性位点残基（AD结构域的Asn 153和Leu 211; OB结构域的Leu 402和Gln 403）对于AsfvLIG的催化效率至关重要。这些独特的结构特征可以作为小分子设计的潜在靶标，这可能会损害ASFV的基因组修复，并有助于未来对抗这种病毒。
African swine fever virus (ASFV) is contagious and can cause highly lethal disease in pigs. ASFV DNA ligase (AsfvLIG) is one of the most error-prone ligases identified to date; it catalyzes DNA joining reaction during DNA repair process of ASFV and plays important roles in mutagenesis of the viral genome. Here, we report four AsfvLIG: DNA complex structures and demonstrate that AsfvLIG has a unique N-terminal domain (NTD) that plays critical roles in substrate binding and catalytic complex assembly. In combination with mutagenesis, in vitro binding and catalytic assays, our study reveals that four unique active site residues (Asn153 and Leu211 of the AD domain; Leu402 and Gln403 of the OB domain) are crucial for the catalytic efficiency of AsfvLIG. These unique structural features can serve as potential targets for small molecule design, which could impair genome repair in ASFV and help combat this virus in the future.