Substrate profiling of Zika virus NS2B-NS3 protease
Substrate profiling of Zika virus NS2B-NS3 protease
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DOI：
10.1002/1873-3468.12443
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发表时间：
2016-10-01
期刊：
影响因子：
3.5
通讯作者：
Pyrc, Krzysztof
中科院分区：
文献类型：
--
作者：
Gruba, Natalia;Martinez, Jose Ignacio Rodriguez;Pyrc, Krzysztof
寨卡病毒（ZIKV）于1947年从乌干达的猕猴中分离出来，当时并不被认为是危险的人类病原体。然而，这种观点最近发生了变化，因为ZIKV感染现在与严重的病理性疾病相关，包括小头畸形和格林-巴利综合征。与黄病毒科中的其他病毒类似，ZIKV表达丝氨酸蛋白酶NS 3，其负责病毒蛋白质加工和复制。在本文中，我们报告了在原核表达系统中与NS 2B辅因子（NS 2B（LN）NS 3（pro））融合的活性NS 3（pro）结构域的表达，并描述了其对合成的FRET型底物文库的特异性。我们的发现为筛选NS 3的潜在细胞内底物和开发这种ZIKV蛋白酶的特异性抑制剂铺平了道路。
Zika virus (ZIKV), isolated from macaques in Uganda in 1947, was not considered to be a dangerous human pathogen. However, this view has recently changed as ZIKV infections are now associated with serious pathological disorders including microcephaly and Guillain-Barre syndrome. Similar to other viruses in the Flaviviridae family, ZIKV expresses the serine protease NS3 which is responsible for viral protein processing and replication. Herein, we report the expression of an active NS3(pro) domain fused with the NS2B cofactor (NS2B(LN)NS3(pro)) in a prokaryotic expression system and profile its specificity for synthesized FRET-type substrate libraries. Our findings pave way for screening potential intracellular substrates of NS3 and for developing specific inhibitors of this ZIKV protease.