2hcs
Crystal structure of RNA dependant RNA polymerase domain of West Nile virus
|
OverviewOverview
Viruses 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.
About this StructureAbout this Structure
2HCS is a Single protein structure of sequence from Kunjin virus with as ligand. Active as RNA-directed RNA polymerase, with EC number 2.7.7.48 Full crystallographic information is available from OCA.
ReferenceReference
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;282(14):10678-89. Epub 2007 Feb 7. PMID:17287213
Page seeded by OCA on Wed Jan 23 13:48:58 2008