Substrate profiling of Zika virus NS2B-NS3 protease

被引：45

作者：

Gruba, Natalia ^{[1
]}

Martinez, Jose Ignacio Rodriguez ^{[2
]}

Grzywa, Renata ^{[3
]}

Wysocka, Magdalena ^{[1
]}

Skorenski, Marcin ^{[3
]}

Burmistrz, Michal ^{[2
,4
]}

Lecka, Maria ^{[3
]}

Lesner, Adam ^{[1
]}

Sienczyk, Marcin ^{[3
]}

Pyrc, Krzysztof ^{[2
,4
]}

机构：

[1] Univ Gdansk, Fac Chem, Dept Biochem, Wita Stwosza 63, PL-80952 Gdansk, Poland

[2] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Microbiol, Krakow, Poland

[3] Wroclaw Univ Sci & Technol, Fac Chem, Div Med Chem & Microbiol, Wybrzeze Wyspianskiego 27, PL-50370 Wroclaw, Poland

[4] Jagiellonian Univ, Malopolska Ctr Biotechnol, Krakow, Poland

来源：

FEBS LETTERS | 2016年 / 590卷 / 20期

关键词：

combinatorial chemistry; NS2B-NS3; protease; substrate library; substrate mapping; Zika virus; DENGUE VIRUS; NS3; PROTEASE; NS2B/NS3; SERINE-PROTEASE; LIGAND DOCKING; AMINO-ACIDS; DRUG DESIGN; SPECIFICITY; INHIBITORS; PROSPECTS;

D O I：

10.1002/1873-3468.12443

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：3459 / 3468

页数：10

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