1H, 13C, and 15N backbone chemical shift assignments of the apo and the ADP-ribose bound forms of the macrodomain of SARS-CoV-2 non-structural protein 3b.
Biomol NMR Assign
; 14(2): 339-346, 2020 10.
Article
in English
| MEDLINE | ID: covidwho-716391
ABSTRACT
The SARS-CoV-2 genome encodes for approximately 30 proteins. Within the international project COVID19-NMR, we distribute the spectroscopic analysis of the viral proteins and RNA. Here, we report NMR chemical shift assignments for the protein Nsp3b, a domain of Nsp3. The 217-kDa large Nsp3 protein contains multiple structurally independent, yet functionally related domains including the viral papain-like protease and Nsp3b, a macrodomain (MD). In general, the MDs of SARS-CoV and MERS-CoV were suggested to play a key role in viral replication by modulating the immune response of the host. The MDs are structurally conserved. They most likely remove ADP-ribose, a common posttranslational modification, from protein side chains. This de-ADP ribosylating function has potentially evolved to protect the virus from the anti-viral ADP-ribosylation catalyzed by poly-ADP-ribose polymerases (PARPs), which in turn are triggered by pathogen-associated sensing of the host immune system. This renders the SARS-CoV-2 Nsp3b a highly relevant drug target in the viral replication process. We here report the near-complete NMR backbone resonance assignment (1H, 13C, 15N) of the putative Nsp3b MD in its apo form and in complex with ADP-ribose. Furthermore, we derive the secondary structure of Nsp3b in solution. In addition, 15N-relaxation data suggest an ordered, rigid core of the MD structure. These data will provide a basis for NMR investigations targeted at obtaining small-molecule inhibitors interfering with the catalytic activity of Nsp3b.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Apoproteins
/
Adenosine Diphosphate Ribose
/
Viral Nonstructural Proteins
/
Carbon-13 Magnetic Resonance Spectroscopy
/
Proton Magnetic Resonance Spectroscopy
/
Betacoronavirus
/
Nitrogen Isotopes
Language:
English
Journal:
Biomol NMR Assign
Journal subject:
Molecular Biology
/
Nuclear Medicine
Year:
2020
Document Type:
Article
Affiliation country:
S12104-020-09973-4
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