Cantini, F. ; Banci, L. ; Altincekic, N. ; Bains, J. K. ; Dhamotharan, K. ; Fuks, C. ; Fürtig, B. ; Gande, S. L. ; Hargittay, B. ; Hengesbach, M. ; Hutchison, M. T. ; Korn, S. M. ; Kubatova, N. ; Kutz, F. ; Linhard, V. ; Löhr, F. ; Meiser, N. ; Pyper, D. J. ; Qureshi, N. S. ; Richter, C. ; Saxena, K. ; Schlundt, A. ; Schwalbe, H. ; Sreeramulu, S. ; Tants, J.-N. ; Wacker, A. ; Weigand, J. E. ; Wöhnert, J. ; Tsika, A. C. ; Fourkiotis, N. K. ; Spyroulias, G. A. (2020)
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.
In: Biomolecular NMR Assignments, 14 (2)
doi: 10.1007/s12104-020-09973-4
Artikel, Bibliographie

Kurzbeschreibung (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.

Typ des Eintrags:	Artikel
Erschienen:	2020
Autor(en):	Cantini, F. ; Banci, L. ; Altincekic, N. ; Bains, J. K. ; Dhamotharan, K. ; Fuks, C. ; Fürtig, B. ; Gande, S. L. ; Hargittay, B. ; Hengesbach, M. ; Hutchison, M. T. ; Korn, S. M. ; Kubatova, N. ; Kutz, F. ; Linhard, V. ; Löhr, F. ; Meiser, N. ; Pyper, D. J. ; Qureshi, N. S. ; Richter, C. ; Saxena, K. ; Schlundt, A. ; Schwalbe, H. ; Sreeramulu, S. ; Tants, J.-N. ; Wacker, A. ; Weigand, J. E. ; Wöhnert, J. ; Tsika, A. C. ; Fourkiotis, N. K. ; Spyroulias, G. A.
Art des Eintrags:	Bibliographie
Titel:	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
Sprache:	Englisch
Publikationsjahr:	Oktober 2020
Ort:	Dordrecht
Verlag:	Springer Netherlands
Titel der Zeitschrift, Zeitung oder Schriftenreihe:	Biomolecular NMR Assignments
Jahrgang/Volume einer Zeitschrift:	14
(Heft-)Nummer:	2
DOI:	10.1007/s12104-020-09973-4
Zugehörige Links:	TUprints Zweitveröffentlichung
Kurzbeschreibung (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.
Freie Schlagworte:	SARS-CoV-2, Non-structural protein, Macrodomain, Solution NMR-spectroscopy, Protein drugability, COVID19-NMR
Sachgruppe der Dewey Dezimalklassifikatin (DDC):	500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit
Fachbereich(e)/-gebiet(e):	10 Fachbereich Biologie 10 Fachbereich Biologie > RNA Biochemie
Hinterlegungsdatum:	19 Dez 2024 09:34
Letzte Änderung:	19 Dez 2024 12:27
PPN:	524853290
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• 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. (deposited 18 Dez 2024 12:55)
  • 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. (deposited 19 Dez 2024 09:34) [Gegenwärtig angezeigt]

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