Crystal Structure of the Dengue Virus RNA-Dependent RNA Polymerase Catalytic Domain at 1.85-Angstrom Resolution

• DOI: 10.1128/jvi.02283-06
• Publication Date: 2007-02-15T01:28:51Z
• Authors: Thai Leong Yap; Ting Xu; Yen-Liang Chen; Helene Malet; Marie-Pierre Egloff; Bruno Canard; Subhash G. Vasudevan; Julien Lescar
• Keywords: Flavivirus

Dengue fever, a neglected emerging disease for which no vaccine or antiviral agents exist at present, is caused by dengue virus, member of the Flavivirus genus, includes several important human pathogens, such as yellow fever and West Nile viruses. The NS5 protein from virus bifunctional contains 900 amino acids. S-adenosyl methionine transferase activity resides within its N-terminal domain, residues 270 to form RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with synthesis minus-strand positive-strand genome, subsequently used template synthesizing additional plus-strand genomes. This essential function production new viral particles catalyzed RdRp. Here we present high-throughput in vitro assay partly recapitulating this crystallographic structure an enzymatically active fragment RdRp refined 1.85-A resolution. nuclear localization sequences, previously thought fold into separate integral part subdomains. also reveals presence two zinc ion binding motifs. In absence strand, chain-terminating nucleoside analogue binds priming loop site. These results should inform accelerate structure-based design compounds against virus.