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

被引：33

作者：

Jain, Rinku ^{[1
]}

Butler, Kyle V. ^{[1
]}

Coloma, Javier ^{[1
]}

Jin, Jian ^{[1
]}

Aggarwal, Aneel K. ^{[1
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Pharmacol Sci, 1425 Madison Ave, New York, NY 10029 USA

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

美国国家卫生研究院;

关键词：

NS5; METHYLTRANSFERASE; VIRUS; VALIDATION; TRANSMISSION; INHIBITORS;

D O I：

10.1038/s41598-017-01756-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The Zika virus (ZIKV) has emerged as a major health hazard. We present here a high resolution structure (1.55 angstrom) 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.

引用

页数：8

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