Abstract
The nonstructural protein 3 (NS3) of hepatitis C virus contains a protease domain at its amino terminus and RNA helicase domain at its carboxyl terminus. To identify optimal NS3 protein for developing screening assays, we expressed full-length NS3 protease/helicase and helicase domains from both HCV type 1a (H77 strain) and 1b (Con1 strain), using either E. coli or baculovirus expression systems. Our studies showed that the full-length NS3 proteins, either with or without the presence of the NS4A domain, from either strains were at least 10-fold more efficient than the corresponding helicase domains in unwinding partial duplex RNA substrates. These findings provide a rationale for the use of full-length NS3 in high throughput screening assays to identify potent small molecule inhibitors of this important target of HCV.
Keywords: hcv, ns, protease domain, helicase domain, coli, baculovirus, unwinding activity
Protein & Peptide Letters
Title: The RNA-Unwinding Activity of Hepatitis C Virus Non-Structural Protein 3 (NS3) Is Positively Modulated by Its Protease Domain
Volume: 12 Issue: 4
Author(s): Baohua Gu, Cynthia M. Pruss, Adam T. Gates and Sanjay S. Khandekar
Affiliation:
Keywords: hcv, ns, protease domain, helicase domain, coli, baculovirus, unwinding activity
Abstract: The nonstructural protein 3 (NS3) of hepatitis C virus contains a protease domain at its amino terminus and RNA helicase domain at its carboxyl terminus. To identify optimal NS3 protein for developing screening assays, we expressed full-length NS3 protease/helicase and helicase domains from both HCV type 1a (H77 strain) and 1b (Con1 strain), using either E. coli or baculovirus expression systems. Our studies showed that the full-length NS3 proteins, either with or without the presence of the NS4A domain, from either strains were at least 10-fold more efficient than the corresponding helicase domains in unwinding partial duplex RNA substrates. These findings provide a rationale for the use of full-length NS3 in high throughput screening assays to identify potent small molecule inhibitors of this important target of HCV.
Export Options
About this article
Cite this article as:
Gu Baohua, Pruss M. Cynthia, Gates T. Adam and Khandekar S. Sanjay, The RNA-Unwinding Activity of Hepatitis C Virus Non-Structural Protein 3 (NS3) Is Positively Modulated by Its Protease Domain, Protein & Peptide Letters 2005; 12 (4) . https://dx.doi.org/10.2174/0929866053765716
DOI https://dx.doi.org/10.2174/0929866053765716 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Molecular Pharmacology of Malignant Pleural Mesothelioma: Challenges and Perspectives From Preclinical and Clinical Studies
Current Drug Targets Mitochondrial DNA Mutations in Cancer: A Review
Current Topics in Medicinal Chemistry Signaling Intermediates (PI3K/PTEN/AKT/mTOR and RAF/MEK/ERK Pathways) as Therapeutic Targets for Anti-Cancer and Anti-Angiogenesis Treatments
Current Signal Transduction Therapy Synthesis, EGFR Inhibition and Anti-cancer Activity of New 3,6-dimethyl-1-phenyl-4-(substituted-methoxy)pyrazolo[3,4-d] pyrimidine Derivatives
Anti-Cancer Agents in Medicinal Chemistry Oxidative Stress and its Clinical Consequences: Relationship between Diabetes and Cancer
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Ex Vivo Gene Therapy and Vision
Current Gene Therapy Regulation of MET Receptor Signaling by SOCS1 and its Implications for Hepatocellular Carcinoma
Current Pharmaceutical Design Gene Transfer to the Central Nervous System: Current State of the Art of the Viral Vectors
Current Genomics In Vivo Anticancer Activity, Toxicology and Histopathological Studies of the Thiolate Gold(I) Complex [Au(Spyrimidine)(PTA-CH<sub>2</sub>Ph)]Br
Anti-Cancer Agents in Medicinal Chemistry Synthetic and Natural Coumarins as Cytotoxic Agents
Current Medicinal Chemistry - Anti-Cancer Agents Multifunctional Radiolabeled Nanoparticles for Targeted Therapy
Current Medicinal Chemistry The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases
Current Molecular Pharmacology Neddylation Pathway as a Novel Anti-cancer Target: Mechanistic Investigation and Therapeutic Implication
Anti-Cancer Agents in Medicinal Chemistry Management of Antineutrophil Cytoplasmic Antibody Associated Vasculitis
Current Immunology Reviews (Discontinued) 2-Arylbenzimidazoles as Antiviral and Antiproliferative Agents-Part 2
Medicinal Chemistry Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise
Current Pharmaceutical Design The Frequency of Thrombotic Events Among Adults Given Antifibrinolytic Drugs for Spontaneous Bleeding: Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials
Current Drug Safety Roles of Epithelial-Mesenchymal Transition in Cancer Drug Resistance
Current Cancer Drug Targets Amino Acid Derived Prodrugs: An Approach to Improve the Bioavailability of Clinically Approved Drugs
Current Topics in Medicinal Chemistry Phosphoproteomics as a Promising Tool for Broadening the Analysis of Clinical Samples and for the Fight Against Cancer Disease
Current Pharmaceutical Analysis