ArticlePLoS computational biology2018
Allostery in the dengue virus NS3 helicase: Insights into the NTPase cycle from molecular simulations.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 46 citations in OpenAlex.
- Allosteric Regulation of RNA Affinity by Motif V-VI Coupling in West Nile Virus NS3 Helicase.Proteins · 2026Article
- NS5 polymerase stimulates RNA duplex unwinding by the Orthoflavivirus NS3 helicase.The Journal of biological chemistry · 2026Article
- Mechanochemical Decoupling of ATP Hydrolysis and RNA Translocation in SARS-CoV-2 nsp13 by the L405D Mutation.bioRxiv : the preprint server for biology · 2026Article
- Article
- Unwinding of an RNA duplex by the Orthoflavivirus NS3 helicase requires translocation beyond the displaced strand and is stimulated by the NS5 RdRp.bioRxiv : the preprint server for biology · 2026Article
- An investigation of fucoidan as a potential inhibitor against DENV/NS3 proteases through molecular dynamics simulations and DFT studies.Journal of molecular modeling · 2025Article
- Motif-VI loop acts as a nucleotide valve in the West Nile Virus NS3 Helicase.Nucleic acids research · 2024Article
- Role of ATP Hydrolysis and Product Release in the Translocation Mechanism of SARS-CoV-2 NSP13.The journal of physical chemistry. B · 2024Article
- Exploring the Targets of Dengue Virus and Designs of Potential Inhibitors.Combinatorial chemistry & high throughput screening · 2024Article
- Impact of bound ssRNA length on allostery in the Dengue Virus NS3 helicase.Nucleic acids research · 2023Article
- Thermodynamic and mechanistic analysis of the functional properties of dengue virus NS3 helicase.Biophysical reviews · 2023Review
- Allosteric crosstalk in modular proteins: Function fine-tuning and drug design.Computational and structural biotechnology journal · 2023Review
- Dengue Virus NS4b N-Terminus Disordered Region Interacts with NS3 Helicase C-Terminal Subdomain to Enhance Helicase Activity.Viruses · 2022Article
- Conserved motifs in the flavivirus NS3 RNA helicase enzyme.Wiley interdisciplinary reviews. RNA · 2022Review
- Modeling Catalysis in Allosteric Enzymes: Capturing Conformational Consequences.Topics in catalysis · 2022Article
- Article
- Molecular dynamics of the viral life cycle: progress and prospects.Current opinion in virology · 2021Review
- Flavivirus enzymes and their inhibitors.The Enzymes · 2021Article
- ATP Analogues for Structural Investigations: Case Studies of a DnaB Helicase and an ABC Transporter.Molecules (Basel, Switzerland) · 2020Review
- A Hyperactive Kunjin Virus NS3 Helicase Mutant Demonstrates Increased Dissemination and Mortality in Mosquitoes.Journal of virology · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The C-terminus domain of non-structural 3 (NS3) protein of the Flaviviridae viruses (e.g. HCV, dengue, West Nile, Zika) is a nucleotide triphosphatase (NTPase) -dependent superfamily 2 (SF2) helicase that unwinds double-stranded RNA while translocating along the nucleic polymer. Due to these functions, NS3 is an important target for antiviral development yet the biophysics of this enzyme are poorly understood. Microsecond-long molecular dynamic simulations of the dengue NS3 helicase domain are reported from which allosteric effects of RNA and NTPase substrates are observed. The presence of a bound single-stranded RNA catalytically enhances the phosphate hydrolysis reaction by affecting the dynamics and positioning of waters within the hydrolysis active site. Coupled with results from the simulations, electronic structure calculations of the reaction are used to quantify this enhancement to be a 150-fold increase, in qualitative agreement with the experimental enhancement factor of 10-100. Additionally, protein-RNA interactions exhibit NTPase substrate-induced allostery, where the presence of a nucleotide (e.g. ATP or ADP) structurally perturbs residues in direct contact with the phosphodiester backbone of the RNA. Residue-residue network analyses highlight pathways of short ranged interactions that connect the two active sites. These analyses identify motif V as a highly connected region of protein structure through which energy released from either active site is hypothesized to move, thereby inducing the observed allosteric effects. These results lay the foundation for the design of novel allosteric inhibitors of NS3.
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