{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:12:50Z","timestamp":1791234770851,"version":"4.1.0"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Dengue fever, a neglected emerging disease for which no vaccine or antiviral agents exist at present, is caused by dengue virus, a member of the\n                    <jats:italic>Flavivirus<\/jats:italic>\n                    genus, which includes several important human pathogens, such as yellow fever and West Nile viruses. The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The\n                    <jats:italic>S<\/jats:italic>\n                    -adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-A\u030a resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus.\n                  <\/jats:p>","DOI":"10.1128\/jvi.02283-06","type":"journal-article","created":{"date-parts":[[2007,2,14]],"date-time":"2007-02-14T20:28:51Z","timestamp":1171484931000},"page":"4753-4765","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":408,"title":["Crystal Structure of the Dengue Virus RNA-Dependent RNA Polymerase Catalytic Domain at 1.85-Angstrom Resolution"],"prefix":"10.1128","volume":"81","author":[{"given":"Thai Leong","family":"Yap","sequence":"first","affiliation":[{"name":"Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos Building, Singapore 138670, Singapore"},{"name":"School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Xu","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos Building, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos Building, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Malet","sequence":"additional","affiliation":[{"name":"AFMB, CNRS, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Pierre","family":"Egloff","sequence":"additional","affiliation":[{"name":"AFMB, CNRS, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Canard","sequence":"additional","affiliation":[{"name":"AFMB, CNRS, Marseille, 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