Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus |
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| Authors: | Erbel Paul Schiering Nikolaus D'Arcy Allan Renatus Martin Kroemer Markus Lim Siew Pheng Yin Zheng Keller Thomas H Vasudevan Subhash G Hommel Ulrich |
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| Affiliation: | Novartis Institutes for Biomedical Research, Protease Platform, 4002 Basel, Switzerland. |
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| 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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