Structures of NS5 Methyltransferase from Zika Virus

被引：79

作者：

Coloma, Javier ^{[1
]}

Jain, Rinku ^{[1
]}

Rajashankar, Kanagalaghatta R. ^{[2
,3
]}

Garcia-Sastre, Adolfo ^{[4
,5
,6
]}

Aggarwal, Aneel K. ^{[1
]}

机构：

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

[2] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA

[3] Adv Photon Source, NE CAT, Argonne, IL 60439 USA

[4] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[5] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA

[6] Icahn Sch Med Mt Sinai, Div Infect Dis, Dept Med, New York, NY 10029 USA

来源：

CELL REPORTS | 2016年 / 16卷 / 12期

关键词：

CRYSTAL-STRUCTURE; RNA CAP; DOMAIN; RECOGNITION; METHYLATION; INHIBITION; VALIDATION;

D O I：

10.1016/j.celrep.2016.08.091

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The Zika virus (ZIKV) poses a major public health emergency. To aid in the development of antivirals, we present two high-resolution crystal structures of the ZIKV NS5 methyltransferase: one bound to S-adenosylmethionine (SAM) and the other bound to SAM and 7-methyl guanosine diphosphate (7-MeGpp). We identify features of ZIKV NS5 methyltransferase that lend to structure-based antiviral drug discovery. Specifically, SAM analogs with functionalities on the Cb atom of the methionine portion of the molecules that occupy the RNA binding tunnel may provide better specificity relative to human RNA methyltransferases.

引用

页码：3097 / 3102

页数：6

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