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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Crystallization
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Dengue Virus / chemistry
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Dengue Virus / enzymology*
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Dengue Virus / genetics
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Dimerization
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / metabolism
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Models, Molecular
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RNA-Dependent RNA Polymerase / antagonists & inhibitors
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RNA-Dependent RNA Polymerase / chemistry*
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RNA-Dependent RNA Polymerase / genetics
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RNA-Dependent RNA Polymerase / metabolism
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Viral Proteins / antagonists & inhibitors
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Viral Proteins / chemistry*
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Viral Proteins / genetics
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Viral Proteins / metabolism
Substances
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Enzyme Inhibitors
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Viral Proteins
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RNA-Dependent RNA Polymerase