2J7W

Dengue virus NS5 RNA dependent RNA polymerase domain complexed with 3' dGTP

2J7W の概要

• エントリーDOI: 10.2210/pdb2j7w/pdb
• 分子名称: POLYPROTEIN, ZINC ION, GUANOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: nucleoside binding site, rna-dependent rna polymerase, dengue, flavivirus, high-throughput assay, viral protein
• 由来する生物種: DENGUE VIRUS
• 細胞内の位置: Envelope protein E: Virion membrane; Multi- pass membrane protein: Q6DLV0
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 74356.93

構造登録者

Yap, T.L.,Xu, T.,Chen, Y.L.,Malet, H.,Egloff, M.P.,Canard, B.,Vasudevan, S.G.,Lescar, J. (登録日: 2006-10-17, 公開日: 2007-03-13, 最終更新日: 2023-12-13)

主引用文献

Yap, T.L.,Xu, T.,Chen, Y.L.,Malet, H.,Egloff, M.P.,Canard, B.,Vasudevan, S.G.,Lescar, J.
Crystal Structure of the Dengue Virus RNA- Dependent RNA Polymerase Catalytic Domain at 1.85 Angstrom Resolution.
J.Virol., 81:4753-, 2007

PubMed Abstract: 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 Flavivirus 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 S-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 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.

PubMed: 17301146
DOI: 10.1128/JVI.02283-06

実験手法

X-RAY DIFFRACTION (2.6 Å)