Structural plasticity of SARS-CoV-2 3CL M(pro) active site cavity revealed by room temperature X-ray crystallography

The COVID-19 disease caused by the SARS-CoV-2 coronavirus has become a pandemic health crisis. An attractive target for antiviral inhibitors is the main protease 3CL M(pro) due to its essential role in processing the polyproteins translated from viral RNA. Here we report the room temperature X-ray s...

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Autores principales: Kneller, Daniel W., Phillips, Gwyndalyn, O’Neill, Hugh M., Jedrzejczak, Robert, Stols, Lucy, Langan, Paul, Joachimiak, Andrzej, Coates, Leighton, Kovalevsky, Andrey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314768/
https://www.ncbi.nlm.nih.gov/pubmed/32581217
http://dx.doi.org/10.1038/s41467-020-16954-7
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author Kneller, Daniel W.
Phillips, Gwyndalyn
O’Neill, Hugh M.
Jedrzejczak, Robert
Stols, Lucy
Langan, Paul
Joachimiak, Andrzej
Coates, Leighton
Kovalevsky, Andrey
author_facet Kneller, Daniel W.
Phillips, Gwyndalyn
O’Neill, Hugh M.
Jedrzejczak, Robert
Stols, Lucy
Langan, Paul
Joachimiak, Andrzej
Coates, Leighton
Kovalevsky, Andrey
author_sort Kneller, Daniel W.
collection PubMed
description The COVID-19 disease caused by the SARS-CoV-2 coronavirus has become a pandemic health crisis. An attractive target for antiviral inhibitors is the main protease 3CL M(pro) due to its essential role in processing the polyproteins translated from viral RNA. Here we report the room temperature X-ray structure of unliganded SARS-CoV-2 3CL M(pro), revealing the ligand-free structure of the active site and the conformation of the catalytic site cavity at near-physiological temperature. Comparison with previously reported low-temperature ligand-free and inhibitor-bound structures suggest that the room temperature structure may provide more relevant information at physiological temperatures for aiding in molecular docking studies.
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spelling pubmed-73147682020-06-26 Structural plasticity of SARS-CoV-2 3CL M(pro) active site cavity revealed by room temperature X-ray crystallography Kneller, Daniel W. Phillips, Gwyndalyn O’Neill, Hugh M. Jedrzejczak, Robert Stols, Lucy Langan, Paul Joachimiak, Andrzej Coates, Leighton Kovalevsky, Andrey Nat Commun Article The COVID-19 disease caused by the SARS-CoV-2 coronavirus has become a pandemic health crisis. An attractive target for antiviral inhibitors is the main protease 3CL M(pro) due to its essential role in processing the polyproteins translated from viral RNA. Here we report the room temperature X-ray structure of unliganded SARS-CoV-2 3CL M(pro), revealing the ligand-free structure of the active site and the conformation of the catalytic site cavity at near-physiological temperature. Comparison with previously reported low-temperature ligand-free and inhibitor-bound structures suggest that the room temperature structure may provide more relevant information at physiological temperatures for aiding in molecular docking studies. Nature Publishing Group UK 2020-06-24 /pmc/articles/PMC7314768/ /pubmed/32581217 http://dx.doi.org/10.1038/s41467-020-16954-7 Text en © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kneller, Daniel W.
Phillips, Gwyndalyn
O’Neill, Hugh M.
Jedrzejczak, Robert
Stols, Lucy
Langan, Paul
Joachimiak, Andrzej
Coates, Leighton
Kovalevsky, Andrey
Structural plasticity of SARS-CoV-2 3CL M(pro) active site cavity revealed by room temperature X-ray crystallography
title Structural plasticity of SARS-CoV-2 3CL M(pro) active site cavity revealed by room temperature X-ray crystallography
title_full Structural plasticity of SARS-CoV-2 3CL M(pro) active site cavity revealed by room temperature X-ray crystallography
title_fullStr Structural plasticity of SARS-CoV-2 3CL M(pro) active site cavity revealed by room temperature X-ray crystallography
title_full_unstemmed Structural plasticity of SARS-CoV-2 3CL M(pro) active site cavity revealed by room temperature X-ray crystallography
title_short Structural plasticity of SARS-CoV-2 3CL M(pro) active site cavity revealed by room temperature X-ray crystallography
title_sort structural plasticity of sars-cov-2 3cl m(pro) active site cavity revealed by room temperature x-ray crystallography
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314768/
https://www.ncbi.nlm.nih.gov/pubmed/32581217
http://dx.doi.org/10.1038/s41467-020-16954-7
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