2hcs
Crystal structure of RNA dependant RNA polymerase domain of West Nile virusCrystal structure of RNA dependant RNA polymerase domain of West Nile virus
Structural highlights
Evolutionary Conservation![]() Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedViruses of the family Flaviviridae are important human and animal pathogens. Among them, the Flaviviruses dengue (DENV) and West Nile (WNV) cause regular outbreaks with fatal outcomes. The RNA-dependent RNA polymerase (RdRp) activity of the non-structural protein 5 (NS5) is a key activity for viral RNA replication. In this study, crystal structures of enzymatically active and inactive WNV RdRp domains were determined at 3.0- and 2.35-A resolution, respectively. The determined structures were shown to be mostly similar to the RdRps of the Flaviviridae members hepatitis C and bovine viral diarrhea virus, although with unique elements characteristic for the WNV RdRp. Using a reverse genetic system, residues involved in putative interactions between the RNA-cap methyltransferase (MTase) and the RdRp domain of Flavivirus NS5 were identified. This allowed us to propose a model for the structure of the full-length WNV NS5 by in silico docking of the WNV MTase domain (modeled from our previously determined structure of the DENV MTase domain) onto the RdRp domain. The Flavivirus RdRp domain structure determined here should facilitate both the design of anti-Flavivirus drugs and structure-function studies of the Flavivirus replication complex in which the multifunctional NS5 protein plays a central role. Crystal structure of the RNA polymerase domain of the West Nile virus non-structural protein 5.,Malet H, Egloff MP, Selisko B, Butcher RE, Wright PJ, Roberts M, Gruez A, Sulzenbacher G, Vonrhein C, Bricogne G, Mackenzie JM, Khromykh AA, Davidson AD, Canard B J Biol Chem. 2007 Apr 6;282(14):10678-89. Epub 2007 Feb 7. PMID:17287213[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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