title: A multi-step strategy to obtain crystals of the dengue virus RNA-dependent RNA polymerase that diffract to high resolution.
abstract: Dengue virus, a member of the Flaviviridae genus, causes dengue fever, an important emerging disease with several million infections occurring annually for which no effective therapy exists. The viral RNA-dependent RNA polymerase NS5 plays an important role in virus replication and represents an interesting target for the development of specific antiviral compounds. Crystals that diffract to 1.85 A resolution that are suitable for three-dimensional structure determination and thus for a structure-based drug-design program have been obtained using a strategy that included expression screening of naturally occurring serotype variants of the protein, the addition of divalent metal ions and crystal dehydration.
authors.affiliation: Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos Building, Singapore 138670, Singapore.
authors.forename: Thai Leong
authors.initials: TL
authors.lastname: Yap
authors.forename: Yen Liang
authors.initials: YL
authors.lastname: Chen
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.forename: Daying
authors.initials: D
authors.lastname: Wen
authors.forename: Subhash G
authors.initials: SG
authors.lastname: Vasudevan
authors.forename: Julien
authors.initials: J
authors.lastname: Lescar
mesh_terms: D002384:Catalysis; D002413:Cations, Divalent; D002712:Chlorides / Q000737:chemistry; D002852:Chromatography, Ion Exchange; D003460:Crystallization; D018360:Crystallography, X-Ray; D003716:Dengue Virus / Q000201:enzymology*; D015636:Magnesium Chloride / Q000737:chemistry; D017895:Manganese Compounds / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry* / Q000302:isolation & purification; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D002413:Cations, Divalent; D002712:Chlorides; D017895:Manganese Compounds; D014764:Viral Proteins; D015636:Magnesium Chloride; D012324:RNA-Dependent RNA Polymerase; C025340:manganese chloride