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

Abstract 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-fluoropheny...

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Autores principales:	Rinku Jain, Kyle V. Butler, Javier Coloma, Jian Jin, Aneel K. Aggarwal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8868ec6242b34c468df4cb1b113ec0bd
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spelling	oai:doaj.org-article:8868ec6242b34c468df4cb1b113ec0bd2021-12-02T15:05:18ZDevelopment of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase10.1038/s41598-017-01756-72045-2322https://doaj.org/article/8868ec6242b34c468df4cb1b113ec0bd2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01756-7https://doaj.org/toc/2045-2322Abstract 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.Rinku JainKyle V. ButlerJavier ColomaJian JinAneel K. AggarwalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rinku Jain Kyle V. Butler Javier Coloma Jian Jin Aneel K. Aggarwal Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase
description	Abstract 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.
format	article
author	Rinku Jain Kyle V. Butler Javier Coloma Jian Jin Aneel K. Aggarwal
author_facet	Rinku Jain Kyle V. Butler Javier Coloma Jian Jin Aneel K. Aggarwal
author_sort	Rinku Jain
title	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_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_sort	development of a s-adenosylmethionine analog that intrudes the rna-cap binding site of zika methyltransferase
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8868ec6242b34c468df4cb1b113ec0bd
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Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase

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