Substrate profiling of Zika virus NS2B-NS3 protease

FEBS Lett. 2016 Oct;590(20):3459-3468. doi: 10.1002/1873-3468.12443. Epub 2016 Oct 18.

Abstract

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-Barré 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 NS3pro domain fused with the NS2B cofactor (NS2BLN NS3pro ) 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.

Keywords: NS2B-NS3 protease; Zika virus; combinatorial chemistry; substrate library; substrate mapping.

Publication types

  • Letter

MeSH terms

  • Binding Sites
  • Fluorescence Resonance Energy Transfer / methods
  • Humans
  • Models, Molecular
  • Molecular Docking Simulation
  • Peptide Library
  • Protein Binding
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Serine Endopeptidases / chemistry*
  • Serine Endopeptidases / metabolism*
  • Substrate Specificity
  • Viral Nonstructural Proteins / chemistry*
  • Viral Nonstructural Proteins / metabolism*
  • Zika Virus / chemistry
  • Zika Virus / enzymology*

Substances

  • Peptide Library
  • Recombinant Fusion Proteins
  • Viral Nonstructural Proteins
  • Serine Endopeptidases

Associated data

  • GENBANK/YP_002790881.1