Abstract
The replication of flaviviruses requires the correct processing of their polyprotein by the viral NS3 protease (NS3pro). Essential for the activation of NS3pro is a 47-residue region of NS2B. Here we report the crystal structures of a dengue NS2B–NS3pro complex and a West Nile virus NS2B–NS3pro complex with a substrate-based inhibitor. These structures identify key residues for NS3pro substrate recognition and clarify the mechanism of NS3pro activation.
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Acknowledgements
We thank W. Kabsch for advice, E. Pohl for support at the beamline and J. Lescar, J.P. Priestle and J. Eder for critical reading.
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Supplementary information
Supplementary Fig. 1
Genome organization of WNV and DEN polyprotein (PDF 109 kb)
Supplementary Fig. 2
Sequence alignment (PDF 204 kb)
Supplementary Fig. 3
Stereo view of experimental electron density maps (PDF 2021 kb)
Supplementary Fig. 4
Inhibitor binding monitored by NMR (PDF 1059 kb)
Supplementary Table 1
Data collection and refinement statistics (PDF 79 kb)
Supplementary Table 2
Activities of WNV NS3 protease inhibitors (PDF 103 kb)
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Erbel, P., Schiering, N., D'Arcy, A. et al. Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus. Nat Struct Mol Biol 13, 372–373 (2006). https://doi.org/10.1038/nsmb1073
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DOI: https://doi.org/10.1038/nsmb1073
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