The structure of Zika virus NS5 reveals a conserved domain conformation

The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one...

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Autores principales: Wang, Boxiao, Tan, Xiao-Feng, Thurmond, Stephanie, Zhang, Zhi-Min, Lin, Asher, Hai, Rong, Song, Jikui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378951/
https://www.ncbi.nlm.nih.gov/pubmed/28345600
http://dx.doi.org/10.1038/ncomms14763
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author Wang, Boxiao
Tan, Xiao-Feng
Thurmond, Stephanie
Zhang, Zhi-Min
Lin, Asher
Hai, Rong
Song, Jikui
author_facet Wang, Boxiao
Tan, Xiao-Feng
Thurmond, Stephanie
Zhang, Zhi-Min
Lin, Asher
Hai, Rong
Song, Jikui
author_sort Wang, Boxiao
collection PubMed
description The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one of the two alternative conformations of flavivirus NS5 proteins. The activity of this NS5 protein is verified through a de novo RdRp assay on a subgenomic ZIKV RNA template. Importantly, our structural analysis leads to the identification of a potential drug-binding site of ZIKV NS5, which might facilitate the development of novel antivirals for ZIKV.
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spelling pubmed-53789512017-04-11 The structure of Zika virus NS5 reveals a conserved domain conformation Wang, Boxiao Tan, Xiao-Feng Thurmond, Stephanie Zhang, Zhi-Min Lin, Asher Hai, Rong Song, Jikui Nat Commun Article The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one of the two alternative conformations of flavivirus NS5 proteins. The activity of this NS5 protein is verified through a de novo RdRp assay on a subgenomic ZIKV RNA template. Importantly, our structural analysis leads to the identification of a potential drug-binding site of ZIKV NS5, which might facilitate the development of novel antivirals for ZIKV. Nature Publishing Group 2017-03-27 /pmc/articles/PMC5378951/ /pubmed/28345600 http://dx.doi.org/10.1038/ncomms14763 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Wang, Boxiao
Tan, Xiao-Feng
Thurmond, Stephanie
Zhang, Zhi-Min
Lin, Asher
Hai, Rong
Song, Jikui
The structure of Zika virus NS5 reveals a conserved domain conformation
title The structure of Zika virus NS5 reveals a conserved domain conformation
title_full The structure of Zika virus NS5 reveals a conserved domain conformation
title_fullStr The structure of Zika virus NS5 reveals a conserved domain conformation
title_full_unstemmed The structure of Zika virus NS5 reveals a conserved domain conformation
title_short The structure of Zika virus NS5 reveals a conserved domain conformation
title_sort structure of zika virus ns5 reveals a conserved domain conformation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378951/
https://www.ncbi.nlm.nih.gov/pubmed/28345600
http://dx.doi.org/10.1038/ncomms14763
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