Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2
Youngchang Kim, Jacek Wower, and colleagues explore the sequence specificity, metal ion dependence and catalytic mechanism of the Nsp15 endoribonuclease NendoU from SARS-CoV-2. The authors also solve five new crystal structures of the enzyme in complex with 5’UMP, 3’UMP, 5’cGpU, uridine 2′,3′-vanada...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-021-01735-9 |
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doaj-c2e1555f80bc4eb28bc2085247f564862021-02-14T12:27:23ZengNature Publishing GroupCommunications Biology2399-36422021-02-014111110.1038/s42003-021-01735-9Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2Youngchang Kim0Jacek Wower1Natalia Maltseva2Changsoo Chang3Robert Jedrzejczak4Mateusz Wilamowski5Soowon Kang6Vlad Nicolaescu7Glenn Randall8Karolina Michalska9Andrzej Joachimiak10Center for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of ChicagoDepartment of Animal Sciences, Auburn UniversityCenter for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of ChicagoCenter for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of ChicagoCenter for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of ChicagoDepartment of Biochemistry and Molecular Biology, University of ChicagoDepartment of Microbiology, Ricketts Laboratory, University of ChicagoDepartment of Microbiology, Ricketts Laboratory, University of ChicagoDepartment of Microbiology, Ricketts Laboratory, University of ChicagoCenter for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of ChicagoCenter for Structural Genomics of Infectious Diseases, Consortium for Advanced Science and Engineering, University of ChicagoYoungchang Kim, Jacek Wower, and colleagues explore the sequence specificity, metal ion dependence and catalytic mechanism of the Nsp15 endoribonuclease NendoU from SARS-CoV-2. The authors also solve five new crystal structures of the enzyme in complex with 5’UMP, 3’UMP, 5’cGpU, uridine 2′,3′-vanadate (transition state analog) and Tipiracil (uracil mimic), and demonstrate that Tipiracil inhibits SARS-CoV-2 Nsp15 by interacting with the uridine binding pocket in the enzyme’s active site.https://doi.org/10.1038/s42003-021-01735-9 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Youngchang Kim Jacek Wower Natalia Maltseva Changsoo Chang Robert Jedrzejczak Mateusz Wilamowski Soowon Kang Vlad Nicolaescu Glenn Randall Karolina Michalska Andrzej Joachimiak |
| spellingShingle |
Youngchang Kim Jacek Wower Natalia Maltseva Changsoo Chang Robert Jedrzejczak Mateusz Wilamowski Soowon Kang Vlad Nicolaescu Glenn Randall Karolina Michalska Andrzej Joachimiak Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2 Communications Biology |
| author_facet |
Youngchang Kim Jacek Wower Natalia Maltseva Changsoo Chang Robert Jedrzejczak Mateusz Wilamowski Soowon Kang Vlad Nicolaescu Glenn Randall Karolina Michalska Andrzej Joachimiak |
| author_sort |
Youngchang Kim |
| title |
Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2 |
| title_short |
Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2 |
| title_full |
Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2 |
| title_fullStr |
Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2 |
| title_full_unstemmed |
Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2 |
| title_sort |
tipiracil binds to uridine site and inhibits nsp15 endoribonuclease nendou from sars-cov-2 |
| publisher |
Nature Publishing Group |
| series |
Communications Biology |
| issn |
2399-3642 |
| publishDate |
2021-02-01 |
| description |
Youngchang Kim, Jacek Wower, and colleagues explore the sequence specificity, metal ion dependence and catalytic mechanism of the Nsp15 endoribonuclease NendoU from SARS-CoV-2. The authors also solve five new crystal structures of the enzyme in complex with 5’UMP, 3’UMP, 5’cGpU, uridine 2′,3′-vanadate (transition state analog) and Tipiracil (uracil mimic), and demonstrate that Tipiracil inhibits SARS-CoV-2 Nsp15 by interacting with the uridine binding pocket in the enzyme’s active site. |
| url |
https://doi.org/10.1038/s42003-021-01735-9 |
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