The dengue virus NS2B-NS3 protease retains the closed conformation in the complex with BPTI

Wan Na Chen, Karin V. Loscha, Christoph Nitsche, Bim Graham, Gottfried Otting*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    49 Citations (Scopus)

    Abstract

    The C-terminal β-hairpin of NS2B (NS2Bc) in the dengue virus NS2B-NS3 protease is required for full enzymatic activity. In crystal structures without inhibitor and in the complex with bovine pancreatic trypsin inhibitor (BPTI), NS2Bc is displaced from the active site. In contrast, nuclear magnetic resonance (NMR) studies in solution only ever showed NS2Bc in the enzymatically active closed conformation. Here we demonstrate by pseudocontact shifts from a lanthanide tag that NS2Bc remains in the closed conformation also in the complex with BPTI. Therefore, the closed conformation is the best template for drug discovery.

    Original languageEnglish
    Pages (from-to)2206-2211
    Number of pages6
    JournalFEBS Letters
    Volume588
    Issue number14
    DOIs
    Publication statusPublished - 27 Jun 2014

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