Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase.
Development of a S-adenosylmethionine analog that intrudes the RNA-cap binding site of Zika methyltransferase.
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DOI：
10.1038/s41598-017-01756-7
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发表时间：
2017-05-09
影响因子：
4.6
通讯作者：
Aggarwal AK
中科院分区：
文献类型：
--
作者：
Jain R;Butler KV;Coloma J;Jin J;Aggarwal AK
寨卡病毒（ZIKV）已成为主要的健康危害。我们在此展示了 ZIKV NS5 甲基转移酶的高分辨率结构 (1.55 Å)，该酶与新型 S-腺苷甲硫氨酸 (SAM) 类似物结合，其中 4-氟苯基部分取代了甲基。我们发现 4-氟苯基部分延伸到 RNA 结合通道的一部分，该部分通常包含 RNA 帽部分的腺苷 2'OH。新的 SAM 类似物和高分辨率晶体结构共同向开发针对 ZIKV 和其他黄病毒的抗病毒药物迈出了一步。
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.