An inhibition model of BPTI to unlinked dengue virus NS2B-NS3 protease

FEBS Lett. 2014 Aug 25;588(17):2794-9. doi: 10.1016/j.febslet.2014.05.063. Epub 2014 Jun 12.

Abstract

One approach to treating the dengue virus infection is to inhibit its NS2B-NS3 protease that plays a vital role in virus maturation. However, the lack of structural information on the active conformation of the protease hindered related drug design. With a co-expression system, we obtained the active two-component protease in its unlinked form. BPTI shows strong competitive inhibitory activity (Ki = 6.5 nM) against this unlinked protease, which adopts a closed conformation. Based on the biochemical and NMR perturbation information, an inhibition model of BPTI to NS2B-NS3 protease is proposed.

Keywords: Bovine pancreatic trypsin inhibitor; Closed/active conformation; Dengue virus; NMR spectroscopy; NS2B-NS3 protease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aprotinin / metabolism
  • Aprotinin / pharmacology*
  • Binding Sites
  • Binding, Competitive
  • Dengue Virus / enzymology*
  • Models, Molecular*
  • Protease Inhibitors / metabolism
  • Protease Inhibitors / pharmacology*
  • Protein Conformation
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / metabolism*

Substances

  • Protease Inhibitors
  • Aprotinin
  • NS3 protease, dengue virus
  • Serine Endopeptidases