title: Conformational flexibility of the Dengue virus RNA-dependent RNA polymerase revealed by a complex with an inhibitor.
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.
authors: Novartis Institute for Tropical Diseases, Singapore, Singapore.
authors: Christian G
authors: CG
authors: Noble
authors: Siew Pheng
authors: SP
authors: Lim
authors: Yen-Liang
authors: YL
authors: Chen
authors: Chong Wai
authors: CW
authors: Liew
authors: Lijian
authors: L
authors: Yap
authors: Julien
authors: J
authors: Lescar
authors: Pei-Yong
authors: PY
authors: Shi
mesh_terms: D003460:Crystallization; D003716:Dengue Virus / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase