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2′-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography

The genome of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus has a capping modification at the 5′-untranslated region (UTR) to prevent its degradation by host nucleases. These modifications are performed by the Nsp10/14 and Nsp10/16 heterodimers using S-adenosylmethioni...

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Autores principales: Wilamowski, Mateusz, Sherrell, Darren A., Minasov, George, Kim, Youngchang, Shuvalova, Ludmilla, Lavens, Alex, Chard, Ryan, Maltseva, Natalia, Jedrzejczak, Robert, Rosas-Lemus, Monica, Saint, Nickolaus, Foster, Ian T., Michalska, Karolina, Satchell, Karla J. F., Joachimiak, Andrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166198/
https://www.ncbi.nlm.nih.gov/pubmed/33972410
http://dx.doi.org/10.1073/pnas.2100170118
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author Wilamowski, Mateusz
Sherrell, Darren A.
Minasov, George
Kim, Youngchang
Shuvalova, Ludmilla
Lavens, Alex
Chard, Ryan
Maltseva, Natalia
Jedrzejczak, Robert
Rosas-Lemus, Monica
Saint, Nickolaus
Foster, Ian T.
Michalska, Karolina
Satchell, Karla J. F.
Joachimiak, Andrzej
author_facet Wilamowski, Mateusz
Sherrell, Darren A.
Minasov, George
Kim, Youngchang
Shuvalova, Ludmilla
Lavens, Alex
Chard, Ryan
Maltseva, Natalia
Jedrzejczak, Robert
Rosas-Lemus, Monica
Saint, Nickolaus
Foster, Ian T.
Michalska, Karolina
Satchell, Karla J. F.
Joachimiak, Andrzej
author_sort Wilamowski, Mateusz
collection PubMed
description The genome of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus has a capping modification at the 5′-untranslated region (UTR) to prevent its degradation by host nucleases. These modifications are performed by the Nsp10/14 and Nsp10/16 heterodimers using S-adenosylmethionine as the methyl donor. Nsp10/16 heterodimer is responsible for the methylation at the ribose 2′-O position of the first nucleotide. To investigate the conformational changes of the complex during 2′-O methyltransferase activity, we used a fixed-target serial synchrotron crystallography method at room temperature. We determined crystal structures of Nsp10/16 with substrates and products that revealed the states before and after methylation, occurring within the crystals during the experiments. Here we report the crystal structure of Nsp10/16 in complex with Cap-1 analog ((m7)GpppA(m2′-O)). Inhibition of Nsp16 activity may reduce viral proliferation, making this protein an attractive drug target.
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spelling pubmed-81661982021-06-10 2′-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography Wilamowski, Mateusz Sherrell, Darren A. Minasov, George Kim, Youngchang Shuvalova, Ludmilla Lavens, Alex Chard, Ryan Maltseva, Natalia Jedrzejczak, Robert Rosas-Lemus, Monica Saint, Nickolaus Foster, Ian T. Michalska, Karolina Satchell, Karla J. F. Joachimiak, Andrzej Proc Natl Acad Sci U S A Biological Sciences The genome of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus has a capping modification at the 5′-untranslated region (UTR) to prevent its degradation by host nucleases. These modifications are performed by the Nsp10/14 and Nsp10/16 heterodimers using S-adenosylmethionine as the methyl donor. Nsp10/16 heterodimer is responsible for the methylation at the ribose 2′-O position of the first nucleotide. To investigate the conformational changes of the complex during 2′-O methyltransferase activity, we used a fixed-target serial synchrotron crystallography method at room temperature. We determined crystal structures of Nsp10/16 with substrates and products that revealed the states before and after methylation, occurring within the crystals during the experiments. Here we report the crystal structure of Nsp10/16 in complex with Cap-1 analog ((m7)GpppA(m2′-O)). Inhibition of Nsp16 activity may reduce viral proliferation, making this protein an attractive drug target. National Academy of Sciences 2021-05-25 2021-05-10 /pmc/articles/PMC8166198/ /pubmed/33972410 http://dx.doi.org/10.1073/pnas.2100170118 Text en Copyright © 2021 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Wilamowski, Mateusz
Sherrell, Darren A.
Minasov, George
Kim, Youngchang
Shuvalova, Ludmilla
Lavens, Alex
Chard, Ryan
Maltseva, Natalia
Jedrzejczak, Robert
Rosas-Lemus, Monica
Saint, Nickolaus
Foster, Ian T.
Michalska, Karolina
Satchell, Karla J. F.
Joachimiak, Andrzej
2′-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography
title 2′-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography
title_full 2′-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography
title_fullStr 2′-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography
title_full_unstemmed 2′-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography
title_short 2′-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography
title_sort 2′-o methylation of rna cap in sars-cov-2 captured by serial crystallography
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166198/
https://www.ncbi.nlm.nih.gov/pubmed/33972410
http://dx.doi.org/10.1073/pnas.2100170118
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