Journal
FEBS LETTERS
Volume 590, Issue 20, Pages 3459-3468Publisher
WILEY
DOI: 10.1002/1873-3468.12443
Keywords
combinatorial chemistry; NS2B-NS3 protease; substrate library; substrate mapping; Zika virus
Funding
- Ministry of Science and Higher Education Iuventus Plus Programme [IP2012 0556 72]
- National Science Center [UMO-657 2012/07/E/NZ6/01712]
- European Union [POIG.02.01.00-12-064/08]
- Ministry of Science and Higher Education of the Republic of Poland
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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.
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