Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase

The Zika virus (ZIKV) has emerged as a major health hazard. We present here a high resolution structure (1.55 Å) of ZIKV NS5 methyltransferase bound to a novel S-adenosylmethionine (SAM) analog in which a 4-fluorophenyl moiety substitutes for the methyl group. We show that the 4-fluorophenyl moiety...

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Autores principales: Jain, Rinku, Butler, Kyle V., Coloma, Javier, Jin, Jian, Aggarwal, Aneel K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431627/
https://www.ncbi.nlm.nih.gov/pubmed/28487506
http://dx.doi.org/10.1038/s41598-017-01756-7
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author Jain, Rinku
Butler, Kyle V.
Coloma, Javier
Jin, Jian
Aggarwal, Aneel K.
author_facet Jain, Rinku
Butler, Kyle V.
Coloma, Javier
Jin, Jian
Aggarwal, Aneel K.
author_sort Jain, Rinku
collection PubMed
description The Zika virus (ZIKV) has emerged as a major health hazard. We present here a high resolution structure (1.55 Å) of ZIKV NS5 methyltransferase bound to a novel S-adenosylmethionine (SAM) analog in which a 4-fluorophenyl moiety substitutes for the methyl group. We show that the 4-fluorophenyl moiety extends into a portion of the RNA binding tunnel that typically contains the adenosine 2′OH of the RNA-cap moiety. Together, the new SAM analog and the high-resolution crystal structure are a step towards the development of antivirals against ZIKV and other flaviviruses.
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spelling pubmed-54316272017-05-16 Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase Jain, Rinku Butler, Kyle V. Coloma, Javier Jin, Jian Aggarwal, Aneel K. Sci Rep Article The Zika virus (ZIKV) has emerged as a major health hazard. We present here a high resolution structure (1.55 Å) of ZIKV NS5 methyltransferase bound to a novel S-adenosylmethionine (SAM) analog in which a 4-fluorophenyl moiety substitutes for the methyl group. We show that the 4-fluorophenyl moiety extends into a portion of the RNA binding tunnel that typically contains the adenosine 2′OH of the RNA-cap moiety. Together, the new SAM analog and the high-resolution crystal structure are a step towards the development of antivirals against ZIKV and other flaviviruses. Nature Publishing Group UK 2017-05-09 /pmc/articles/PMC5431627/ /pubmed/28487506 http://dx.doi.org/10.1038/s41598-017-01756-7 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jain, Rinku
Butler, Kyle V.
Coloma, Javier
Jin, Jian
Aggarwal, Aneel K.
Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase
title Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase
title_full Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase
title_fullStr Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase
title_full_unstemmed Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase
title_short Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase
title_sort development of a s-adenosylmethionine analog that intrudes the rna-cap binding site of zika methyltransferase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431627/
https://www.ncbi.nlm.nih.gov/pubmed/28487506
http://dx.doi.org/10.1038/s41598-017-01756-7
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