ArticleJournal of virology2004
Herpesvirus protease inhibition by dimer disruption.
Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 61 citations in OpenAlex.
- Conformational Dynamics of Viral Protease Precursors in Maturation, Inhibition, and Drug-Resistance Development.Viruses · 2026Review
- Linking biochemical and cellular efficacy of MERS coronavirus main protease inhibitors.ACS pharmacology & translational science · 2026Article
- Linking biochemical and cellular efficacy of MERS coronavirus main protease inhibitors.bioRxiv : the preprint server for biology · 2026Article
- Molecular mechanisms of protease precursor autoprocessing of RNA viruses: a comprehensive review.Virology journal · 2026Review
- Enzyme kinetics model for the coronavirus main protease including dimerization and ligand binding.Biophysical journal · 2025Article
- Stabilization of a miniprotein fold by an unpuckered proline surrogate.Communications chemistry · 2025Article
- Unexpected Single-Ligand Occupancy and Negative Cooperativity in the SARS-CoV-2 Main Protease.Journal of chemical information and modeling · 2024Article
- Viral proteases as therapeutic targets.Molecular aspects of medicine · 2022Review
- Unraveling a Ligand-Induced Twist of a Homodimeric Enzyme by Pulsed Electron-Electron Double Resonance.Angewandte Chemie (International ed. in English) · 2021Article
- Precursors of Viral Proteases as Distinct Drug Targets.Viruses · 2021Review
- Article
- GII.4 Norovirus Protease Shows pH-Sensitive Proteolysis with a Unique Arg-His Pairing in the Catalytic Site.Journal of virology · 2019Article
- Mechanism of Pseudomonas aeruginosa Small Protease (PASP), a Corneal Virulence Factor.Investigative ophthalmology & visual science · 2018Article
- NS2 proteases from hepatitis C virus and related hepaciviruses share composite active sites and previously unrecognized intrinsic proteolytic activities.PLoS pathogens · 2018Article
- DynaFace: Discrimination between Obligatory and Non-obligatory Protein-Protein Interactions Based on the Complex's Dynamics.PLoS computational biology · 2015Article
- Current and potential treatments for ubiquitous but neglected herpesvirus infections.Chemical reviews · 2014Review
- Broad-spectrum allosteric inhibition of herpesvirus proteases.Biochemistry · 2014Article
- Pathological unfoldomics of uncontrolled chaos: intrinsically disordered proteins and human diseases.Chemical reviews · 2014Review
- Inhibition of caspase-9 by stabilized peptides targeting the dimerization interface.Biopolymers · 2012Article
- A screening strategy for trapping the inactive conformer of a dimeric enzyme with a small molecule inhibitor.Methods in molecular biology (Clifton, N.J.) · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV), like all herpesviruses, encodes a protease (KSHV Pr), which is necessary for the viral lytic cycle. Herpesvirus proteases function as obligate dimers; however, each monomer has an intact, complete active site which does not interact directly with the other monomer across the dimer interface. Protein grafting of an interfacial KSHV Pr alpha-helix onto a small stable protein, avian pancreatic polypeptide, generated a helical 30-amino-acid peptide designed to disrupt the dimerization of KSHV Pr. The chimeric peptide was optimized through protein modeling of the KSHV Pr-peptide complex. Circular dichroism analysis and gel filtration chromatography revealed that the rationally designed peptide adopts a helical conformation and is capable of disrupting KSHV Pr dimerization, respectively. Additionally, the optimized peptide inhibits KSHV Pr activity by 50% at a approximately 200-fold molar excess of peptide to KSHV Pr, and the dissociation constant was estimated to be 300 microM. Mutagenesis of the interfacial residue M197 to a leucine resulted in an inhibitory concentration which was twofold higher for KSHV Pr M197L than for KSHV Pr, in agreement with the model that the dimer interface is involved in peptide binding. These results indicate that the dimer interface, as well as the active sites, of herpesvirus proteases is a viable target for inhibiting enzyme activity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.