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DOI	10.1073/pnas.2004500118
	ADP-ribose and analogues bound to the deMARylating macrodomain from the bat coronavirus HKU4
	Hammond R.G.; Schormann N.; McPherson R.L.; Leung A.K.L.; Deivanayagam C.C.S.; Johnson M.A.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	Macrodomains are proteins that recognize and hydrolyze ADP ribose (ADPR) modifications of intracellular proteins. Macrodomains are implicated in viral genome replication and interference with host cell immune responses. They are important to the infectious cycle of Coronaviridae and Togaviridae viruses. We describe crystal structures of the conserved macrodomain from the bat coronavirus (CoV) HKU4 in complex with ligands. The structures reveal a binding cavity that accommodates ADPR and analogs via local structural changes within the pocket. Using a radioactive assay, we present evidence of mono-ADPR (MAR) hydrolase activity. In silico analysis presents further evidence on recognition of the ADPR modification for hydrolysis. Mutational analysis of residues within the binding pocket resulted in diminished enzymatic activity and binding affinity. We conclude that the common structural features observed in the macrodomain in a bat CoV contribute to a conserved function that can be extended to other known macrodomains. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	ADP-ribose; Coronavirus; Crystal structure; Macrodomain; Viral protein
语种	英语
scopus关键词	adenosine diphosphate ribose; hydrolase; viral protein; adenosine diphosphate ribose; ADPribose pyrophosphatase; inorganic pyrophosphatase; viral protein; ADPR gene; Article; binding affinity; controlled study; Coronavirinae; crystal structure; crystallization; DNA modification; enzyme active site; enzyme activity; gene interaction; genetic conservation; HKU4 gene; hydrolysis; ligand binding; molecular docking; mutational analysis; nonhuman; priority journal; protein domain; Togaviridae; virus gene; animal; bat; binding site; chemistry; Coronavirinae; enzymology; genetics; X ray crystallography; Adenosine Diphosphate Ribose; Animals; Binding Sites; Chiroptera; Coronavirus; Crystallography, X-Ray; Hydrolysis; Pyrophosphatases; Viral Nonstructural Proteins
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181073
作者单位	Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, United States; Department of Molecular Biology and Genetics, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, United States; Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, United States
推荐引用方式 GB/T 7714	Hammond R.G.,Schormann N.,McPherson R.L.,et al. ADP-ribose and analogues bound to the deMARylating macrodomain from the bat coronavirus HKU4[J],2021,118(2).
APA	Hammond R.G.,Schormann N.,McPherson R.L.,Leung A.K.L.,Deivanayagam C.C.S.,&Johnson M.A..(2021).ADP-ribose and analogues bound to the deMARylating macrodomain from the bat coronavirus HKU4.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Hammond R.G.,et al."ADP-ribose and analogues bound to the deMARylating macrodomain from the bat coronavirus HKU4".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).