ArticleThe Journal of biological chemistry2013
NMR analysis of a novel enzymatically active unlinked dengue NS2B-NS3 protease complex.
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 50 papers.
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Who cites it
50 citing papers in PubMed.
- Coupled Binding and Folding of NS2B/NS3 Protease and Linker Effects Revealed by Topology-Based Modeling.The journal of physical chemistry. B · 2026Article
- Coupled Binding and Folding of NS2B/NS3 Protease and Linker Effects Revealed by Topology-based Modeling.bioRxiv : the preprint server for biology · 2026Article
- Interpretable machine learning-driven identification of novel DENV NS2B-NS3 protease inhibitors through multi-stage virtual screening and experimental validation.Molecular diversity · 2026Article
- Zika NS2B Protein: In Vitro Formation of Large Multimeric Networks.International journal of molecular sciences · 2026Article
- Dynamic claw of dengue protease unveils druggability potential with high affinity allosteric inhibitors.PNAS nexus · 2025Article
- Functional Roles and Host Interactions ofPathogens (Basel, Switzerland) · 2025Review
- A Non-Active-Site Inhibitor with Selectivity for Zika Virus NS2B-NS3 Protease.ACS infectious diseases · 2024Article
- Development in the Inhibition of Dengue Proteases as Drug Targets.Current medicinal chemistry · 2024Review
- Combined NMR and molecular dynamics conformational filter identifies unambiguously dynamic ensembles of Dengue protease NS2B/NS3pro.Communications biology · 2023Article
- Designing photoaffinity tool compounds for the investigation of the DENV NS2B-NS3 protease allosteric binding pocket.RSC medicinal chemistry · 2023Article
- Seeking heterocyclic scaffolds as antivirals against dengue virus.European journal of medicinal chemistry · 2022Review
- Dynamic Interactions of Post Cleaved NS2B Cofactor and NS3 Protease Identified by Integrative Structural Approaches.Viruses · 2022Article
- Surgical Strikes on Host Defenses: Role of the Viral Protease Activity in Innate Immune Antagonism.Pathogens (Basel, Switzerland) · 2022Review
- Article
- Antiviral Agents against Flavivirus Protease: Prospect and Future Direction.Pathogens (Basel, Switzerland) · 2022Review
- Review
- Myricetin Allosterically Inhibits the Dengue NS2B-NS3 Protease by Disrupting the Active and Locking the Inactive Conformations.ACS omega · 2022Article
- Structure and Dynamics of Zika Virus Protease and Its Insights into Inhibitor Design.Biomedicines · 2021Review
- Dengue virus protease activity modulated by dynamics of protease cofactor.Biophysical journal · 2021Article
- Article
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19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The dengue virus (DENV) is a mosquito-borne pathogen responsible for an estimated 100 million human infections annually. The viral genome encodes a two-component trypsin-like protease that contains the cofactor region from the nonstructural protein NS2B and the protease domain from NS3 (NS3pro). The NS2B-NS3pro complex plays a crucial role in viral maturation and has been identified as a potential drug target. Using a DENV protease construct containing NS2B covalently linked to NS3pro via a Gly4-Ser-Gly4 linker ("linked protease"), previous x-ray crystal structures show that the C-terminal fragment of NS2B is remote from NS3pro and exists in an open state in the absence of an inhibitor; however, in the presence of an inhibitor, NS2B complexes with NS3pro to form a closed state. This linked enzyme produced NMR spectra with severe signal overlap and line broadening. To obtain a protease construct with a resolved NMR spectrum, we expressed and purified an unlinked protease complex containing a 50-residue segment of the NS2B cofactor region and NS3pro without the glycine linker using a coexpression system. This unlinked protease complex was catalytically active at neutral pH in the absence of glycerol and produced dispersed cross-peaks in a (1)H-(15)N heteronuclear single quantum correlation spectrum that enabled us to conduct backbone assignments using conventional techniques. In addition, titration with an active-site peptide aldehyde inhibitor and paramagnetic relaxation enhancement studies demonstrated that the unlinked DENV protease exists predominantly in a closed conformation in solution. This protease complex can serve as a useful tool for drug discovery against DENV.
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