Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex.
Cellular and viral S-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism, detoxification, signal transduction, chromatin remodeling, nucleic acid processing, and mRNA capping. The Severe Acute Respiratory Syndrome coronavirus nsp16 protein is a...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21637813/?tool=EBI |
| _version_ | 1818574165439938560 |
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| author | Etienne Decroly Claire Debarnot François Ferron Mickael Bouvet Bruno Coutard Isabelle Imbert Laure Gluais Nicolas Papageorgiou Andrew Sharff Gérard Bricogne Miguel Ortiz-Lombardia Julien Lescar Bruno Canard |
| author_facet | Etienne Decroly Claire Debarnot François Ferron Mickael Bouvet Bruno Coutard Isabelle Imbert Laure Gluais Nicolas Papageorgiou Andrew Sharff Gérard Bricogne Miguel Ortiz-Lombardia Julien Lescar Bruno Canard |
| author_sort | Etienne Decroly |
| collection | DOAJ |
| description | Cellular and viral S-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism, detoxification, signal transduction, chromatin remodeling, nucleic acid processing, and mRNA capping. The Severe Acute Respiratory Syndrome coronavirus nsp16 protein is a S-adenosylmethionine-dependent (nucleoside-2'-O)-methyltransferase only active in the presence of its activating partner nsp10. We report the nsp10/nsp16 complex structure at 2.0 Å resolution, which shows nsp10 bound to nsp16 through a ∼930 Ų surface area in nsp10. Functional assays identify key residues involved in nsp10/nsp16 association, and in RNA binding or catalysis, the latter likely through a SN2-like mechanism. We present two other crystal structures, the inhibitor Sinefungin bound in the S-adenosylmethionine binding pocket and the tighter complex nsp10(Y96F)/nsp16, providing the first structural insight into the regulation of RNA capping enzymes in +RNA viruses. |
| first_indexed | 2024-12-15T00:22:55Z |
| format | Article |
| id | doaj.art-5ede7db0af914726a3936efe63df46f1 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-15T00:22:55Z |
| publishDate | 2011-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-5ede7db0af914726a3936efe63df46f12022-12-21T22:42:15ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742011-05-0175e100205910.1371/journal.ppat.1002059Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex.Etienne DecrolyClaire DebarnotFrançois FerronMickael BouvetBruno CoutardIsabelle ImbertLaure GluaisNicolas PapageorgiouAndrew SharffGérard BricogneMiguel Ortiz-LombardiaJulien LescarBruno CanardCellular and viral S-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism, detoxification, signal transduction, chromatin remodeling, nucleic acid processing, and mRNA capping. The Severe Acute Respiratory Syndrome coronavirus nsp16 protein is a S-adenosylmethionine-dependent (nucleoside-2'-O)-methyltransferase only active in the presence of its activating partner nsp10. We report the nsp10/nsp16 complex structure at 2.0 Å resolution, which shows nsp10 bound to nsp16 through a ∼930 Ų surface area in nsp10. Functional assays identify key residues involved in nsp10/nsp16 association, and in RNA binding or catalysis, the latter likely through a SN2-like mechanism. We present two other crystal structures, the inhibitor Sinefungin bound in the S-adenosylmethionine binding pocket and the tighter complex nsp10(Y96F)/nsp16, providing the first structural insight into the regulation of RNA capping enzymes in +RNA viruses.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21637813/?tool=EBI |
| spellingShingle | Etienne Decroly Claire Debarnot François Ferron Mickael Bouvet Bruno Coutard Isabelle Imbert Laure Gluais Nicolas Papageorgiou Andrew Sharff Gérard Bricogne Miguel Ortiz-Lombardia Julien Lescar Bruno Canard Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex. PLoS Pathogens |
| title | Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex. |
| title_full | Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex. |
| title_fullStr | Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex. |
| title_full_unstemmed | Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex. |
| title_short | Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex. |
| title_sort | crystal structure and functional analysis of the sars coronavirus rna cap 2 o methyltransferase nsp10 nsp16 complex |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21637813/?tool=EBI |
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