Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase
oleh: Rinku Jain, Kyle V. Butler, Javier Coloma, Jian Jin, Aneel K. Aggarwal
| Format: | Article |
|---|---|
| Diterbitkan: | Nature Portfolio 2017-05-01 |
Deskripsi
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.