Molecular Basis for ADP-Ribose Binding to the Mac1 Domain of SARS-CoV-2 nsp3

Molecular Basis for ADP-Ribose Binding to the Mac1 Domain of SARS-CoV-2 nsp3
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DOI:
10.1021/acs.biochem.0c00309
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发表时间:
2020-07-21
期刊:
影响因子:
2.9
通讯作者:
Silvaggi, Nicholas R.
Silvaggi, Nicholas R.
中科院分区:
生物学3区
文献类型:
--
作者:
Frick, David N.;Virdi, Rajdeep S.;Silvaggi, Nicholas R.

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导致COVID-19的病毒SARS-CoV-2有一个大的RNA基因组,可以编码许多蛋白质,这些蛋白质可能是抗病毒药物的靶标。其中一些蛋白质,如RNA依赖的RNA聚合酶、解旋酶和主要蛋白酶,在SARS- cov -2和原始SARS病毒之间是保守的,但其他一些蛋白质则不是。这项研究检查了SARS-CoV-2编码的一种最不同的蛋白质,即非结构蛋白3 (nsp3)的大结构域。尽管该SARS-CoV-2大结构域中26%的氨基酸与在其他冠状病毒中观察到的氨基酸不同,但生化和结构数据显示,该蛋白保留了结合adp核糖的能力,这是β冠状病毒的一个重要特征,也是一个潜在的治疗靶点。
The virus that causes COVID-19, SARS-CoV-2, has a large RNA genome that encodes numerous proteins that might be targets for antiviral drugs. Some of these proteins, such as the RNA-dependent RNA polymerase, helicase, and main protease, are well conserved between SARS-CoV-2 and the original SARS virus, but several others are not. This study examines one of the proteins encoded by SARS-CoV-2 that is most different, a macrodomain of nonstructural protein 3 (nsp3). Although 26% of the amino acids in this SARS-CoV-2 macrodomain differ from those observed in other coronaviruses, biochemical and structural data reveal that the protein retains the ability to bind ADP-ribose, which is an important characteristic of beta coronaviruses and a potential therapeutic target.