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Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes
Among 15 nonstructural proteins (Nsps), the newly emerging Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) encodes a large, multidomain Nsp3. One of its units is the ADP-ribose phosphatase domain (ADRP; also known as the macrodomain, MacroD), which is believed to interfere with the host...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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International Union of Crystallography
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467174/ https://www.ncbi.nlm.nih.gov/pubmed/32939273 http://dx.doi.org/10.1107/S2052252520009653 |
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author | Michalska, Karolina Kim, Youngchang Jedrzejczak, Robert Maltseva, Natalia I. Stols, Lucy Endres, Michael Joachimiak, Andrzej |
author_facet | Michalska, Karolina Kim, Youngchang Jedrzejczak, Robert Maltseva, Natalia I. Stols, Lucy Endres, Michael Joachimiak, Andrzej |
author_sort | Michalska, Karolina |
collection | PubMed |
description | Among 15 nonstructural proteins (Nsps), the newly emerging Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) encodes a large, multidomain Nsp3. One of its units is the ADP-ribose phosphatase domain (ADRP; also known as the macrodomain, MacroD), which is believed to interfere with the host immune response. Such a function appears to be linked to the ability of the protein to remove ADP-ribose from ADP-ribosylated proteins and RNA, yet the precise role and molecular targets of the enzyme remain unknown. Here, five high-resolution (1.07–2.01 Å) crystal structures corresponding to the apo form of the protein and its complexes with 2-(N-morpholino)ethanesulfonic acid (MES), AMP and ADP-ribose have been determined. The protein is shown to undergo conformational changes to adapt to the ligand in the manner previously observed in close homologues from other viruses. A conserved water molecule is also identified that may participate in hydrolysis. This work builds foundations for future structure-based research on ADRP, including the search for potential antiviral therapeutics. |
format | Online Article Text |
id | pubmed-7467174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
spelling | pubmed-74671742020-09-15 Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes Michalska, Karolina Kim, Youngchang Jedrzejczak, Robert Maltseva, Natalia I. Stols, Lucy Endres, Michael Joachimiak, Andrzej IUCrJ Research Papers Among 15 nonstructural proteins (Nsps), the newly emerging Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) encodes a large, multidomain Nsp3. One of its units is the ADP-ribose phosphatase domain (ADRP; also known as the macrodomain, MacroD), which is believed to interfere with the host immune response. Such a function appears to be linked to the ability of the protein to remove ADP-ribose from ADP-ribosylated proteins and RNA, yet the precise role and molecular targets of the enzyme remain unknown. Here, five high-resolution (1.07–2.01 Å) crystal structures corresponding to the apo form of the protein and its complexes with 2-(N-morpholino)ethanesulfonic acid (MES), AMP and ADP-ribose have been determined. The protein is shown to undergo conformational changes to adapt to the ligand in the manner previously observed in close homologues from other viruses. A conserved water molecule is also identified that may participate in hydrolysis. This work builds foundations for future structure-based research on ADRP, including the search for potential antiviral therapeutics. International Union of Crystallography 2020-07-17 /pmc/articles/PMC7467174/ /pubmed/32939273 http://dx.doi.org/10.1107/S2052252520009653 Text en © Karolina Michalska et al. 2020 http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Research Papers Michalska, Karolina Kim, Youngchang Jedrzejczak, Robert Maltseva, Natalia I. Stols, Lucy Endres, Michael Joachimiak, Andrzej Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes |
title | Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes |
title_full | Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes |
title_fullStr | Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes |
title_full_unstemmed | Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes |
title_short | Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: from the apo form to ligand complexes |
title_sort | crystal structures of sars-cov-2 adp-ribose phosphatase: from the apo form to ligand complexes |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467174/ https://www.ncbi.nlm.nih.gov/pubmed/32939273 http://dx.doi.org/10.1107/S2052252520009653 |
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