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Conformational flexibility of the Dengue virus RNA-dependent RNA polymerase revealed by a complex with an inhibitor
Christian G Noble1, Siew Pheng Lim, Yen-Liang Chen
1Novartis Institute for Tropical Diseases, Singapore, Singapore.
Abstract:
We report a highly reproducible method to crystallize the RNA-dependent RNA polymerase (RdRp) domain of dengue virus serotype 3 (DENV-3), allowing structure refinement to a 1.79-Å resolution and revealing amino acids not seen previously. We also present a DENV-3 polymerase/inhibitor cocrystal structure at a 2.1-Å resolution. The inhibitor binds to the RdRp as a dimer and causes conformational changes in the protein. The improved crystallization conditions and new structural information should accelerate structure-based drug discovery.
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