ArticleThe Journal of biological chemistry2013
A crystal structure of the dengue virus non-structural protein 5 (NS5) polymerase delineates interdomain amino acid residues that enhance its thermostability and de novo initiation activities.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 87 citations in OpenAlex.
- Computational discovery of DENV-3 RdRp allosteric inhibitors: biological evaluation and mechanistic studies.Molecular diversity · 2026Article
- Identification of potential inhibitors of dengue virus ns5 methyltransferase and polymerase domains through virtual screening and molecular dynamics studies.Journal of molecular modeling · 2026Article
- Exchanging the stem-loop A promoter of Zika virus with the corresponding region of tick-borne encephalitis virus generates a chimeric virus that replicates in vertebrate and mosquito cells.Archives of virology · 2025Article
- Different receptor models show differences in ligand binding strength and location: a computational drug screening for the tick-borne encephalitis virus.Molecular diversity · 2025Article
- Development in the Inhibition of Dengue Proteases as Drug Targets.Current medicinal chemistry · 2024Review
- New oxindole carboxamides as inhibitors of DENV NS5 RdRp: Design, synthesis, docking and Biochemical characterization.Heliyon · 2023Article
- Development of Zika Virus Mini-Replicon Based Single-Round Infectious Particles as Gene Delivery Vehicles.Viruses · 2023Article
- Assessing the potential of NS2B/NS3 protease inhibitors biomarker in curbing dengue virus infections:Frontiers in cellular and infection microbiology · 2023Review
- Identification of new inhibitors of NS5 from dengue virus using saturation transfer difference (STD-NMR) and molecular docking studies.RSC advances · 2022Article
- Identification of 6ω-cyclohexyl-2-(phenylamino carbonylmethylthio)pyrimidin-4(3Frontiers in chemistry · 2022Article
- Virtual Screening of Drug-Like Compounds as Potential Inhibitors of the Dengue Virus NS5 Protein.Frontiers in chemistry · 2022Article
- Review
- Two RNA Tunnel Inhibitors Bind in Highly Conserved Sites in Dengue Virus NS5 Polymerase: Structural and Functional Studies.Journal of virology · 2020Article
- [1,2,4]Triazolo[1,5-a]pyrimidine derivative (Mol-5) is a new NS5-RdRp inhibitor of DENV2 proliferation and DENV2-induced inflammation.Acta pharmacologica Sinica · 2020Article
- A conformation-based intra-molecular initiation factor identified in the flavivirus RNA-dependent RNA polymerase.PLoS pathogens · 2020Article
- Polymerase Activity, Protein-Protein Interaction, and Cellular Localization of the Usutu Virus NS5 Protein.Antimicrobial agents and chemotherapy · 2019Article
- NS5 from Dengue Virus Serotype 2 Can Adopt a Conformation Analogous to That of Its Zika Virus and Japanese Encephalitis Virus Homologues.Journal of virology · 2019Article
- Identification of a Small Interface between the Methyltransferase and RNA Polymerase of NS5 that is Essential for Zika Virus Replication.Scientific reports · 2018Article
- Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerases.Viruses · 2018Review
- Evaluation of Sofosbuvir (β-D-2'-deoxy-2'-α-fluoro-2'-β-C-methyluridine) as an inhibitor of Dengue virus replication<sup/>.Scientific reports · 2017Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
The dengue virus (DENV) non-structural protein 5 (NS5) comprises an N-terminal methyltransferase and a C-terminal RNA-dependent RNA polymerase (RdRp) domain. Both enzymatic activities form attractive targets for antiviral development. Available crystal structures of NS5 fragments indicate that residues 263-271 (using the DENV serotype 3 numbering) located between the two globular domains of NS5 could be flexible. We observed that the addition of linker residues to the N-terminal end of the DENV RdRp core domain stabilizes DENV1-4 proteins and improves their de novo polymerase initiation activities by enhancing the turnover of the RNA and NTP substrates. Mutation studies of linker residues also indicate their importance for viral replication. We report the structure at 2.6-Å resolution of an RdRp fragment from DENV3 spanning residues 265-900 that has enhanced catalytic properties compared with the RdRp fragment (residues 272-900) reported previously. This new orthorhombic crystal form (space group P21212) comprises two polymerases molecules arranged as a dimer around a non-crystallographic dyad. The enzyme adopts a closed "preinitiation" conformation similar to the one that was captured previously in space group C2221 with one molecule per asymmetric unit. The structure reveals that residues 269-271 interact with the RdRp domain and suggests that residues 263-268 of the NS5 protein from DENV3 are the major contributors to the flexibility between its methyltransferase and RdRp domains. Together, these results should inform the screening and development of antiviral inhibitors directed against the DENV RdRp.
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