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...
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oai:doaj.org-article:5ede7db0af914726a3936efe63df46f12021-11-18T06:03:21ZCrystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex.1553-73661553-737410.1371/journal.ppat.1002059https://doaj.org/article/5ede7db0af914726a3936efe63df46f12011-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21637813/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Cellular 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.Etienne DecrolyClaire DebarnotFrançois FerronMickael BouvetBruno CoutardIsabelle ImbertLaure GluaisNicolas PapageorgiouAndrew SharffGérard BricogneMiguel Ortiz-LombardiaJulien LescarBruno CanardPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 5, p e1002059 (2011) |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 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. |
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. |
format |
article |
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 |
title |
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_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_sort |
crystal structure and functional analysis of the sars-coronavirus rna cap 2'-o-methyltransferase nsp10/nsp16 complex. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doaj.org/article/5ede7db0af914726a3936efe63df46f1 |
work_keys_str_mv |
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