Structural, Biophysical, and Biochemical Elucidation of the SARS-CoV-2 Nonstructural Protein 3 Macro Domain
| Autor: | San Chi Chang, Yi Chih Chiu, Bo Chen Jiang, Meng-Hsuan Lin, Tsung Han Wu, Chun-Hua Hsu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
crystal structure Coronavirus disease 2019 (COVID-19) Protein Conformation Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses 030106 microbiology Pneumonia Viral Host response Computational biology Biology Viral Nonstructural Proteins Cleavage (embryo) medicine.disease_cause Viral infection Antiviral Agents Article 03 medical and health sciences Macro domain Betacoronavirus Protein Domains medicine Humans Pandemics Coronavirus Adenosine Diphosphate Ribose SARS-CoV-2 virus diseases COVID-19 Binding ability 030104 developmental biology Infectious Diseases Drug Design macro domain ADP-ribose Coronavirus Infections |
| Zdroj: | ACS Infectious Diseases |
| ISSN: | 2373-8227 |
| DOI: | 10.1021/acsinfecdis.0c00441 |
| Popis: | The pandemic outbreak of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has threatened the global public health and economy since late December 2019. SARS-CoV-2 encodes the conserved macro domain within nonstructural protein 3, which may reverse cellular ADP-ribosylation and potentially cut the signal of a viral infection in the cell. Herein, we report that the SARS-CoV-2 macro domain was examined as a poly-ADP-ribose (ADPR) binding module and possessed mono-ADPR cleavage enzyme activity. After confirming the ADPR binding ability via a biophysical approach, the X-ray crystal structure of the SARS-CoV-2 macro domain was determined and structurally compared with those of other viruses. This study provides structural, biophysical, and biochemical bases to further evaluate the role of the SARS-CoV-2 macro domain in the host response via ADP-ribose binding but also as a potential target for drug design against COVID-19. |
| Databáze: | OpenAIRE |
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