ArticleJournal of molecular biology2007
Substrate modulation of enzyme activity in the herpesvirus protease family.
Article in Journal of molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Enzyme kinetics model for the coronavirus main protease including dimerization and ligand binding.Biophysical journal · 2025Article
- The effect of dimerization and ligand binding on the dynamics of Kaposi's sarcoma-associated herpesvirus protease.Proteins · 2022Article
- Evaluation of A-azepano-triterpenoids and related derivatives as antimicrobial and antiviral agents.The Journal of antibiotics · 2021Article
- (±)-Japonones A and B, two pairs of new enantiomers with anti-KSHV activities from Hypericum japonicum.Scientific reports · 2016Article
- Fragment-Based Protein-Protein Interaction Antagonists of a Viral Dimeric Protease.ChemMedChem · 2016Article
- Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease.PLoS pathogens · 2015Article
- Current and potential treatments for ubiquitous but neglected herpesvirus infections.Chemical reviews · 2014Review
- Broad-spectrum allosteric inhibition of herpesvirus proteases.Biochemistry · 2014Article
- 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
- Enzyme inhibition by allosteric capture of an inactive conformation.Journal of molecular biology · 2011Article
- Inhibition of a viral enzyme by a small-molecule dimer disruptor.Nature chemical biology · 2009Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The herpesvirus proteases are an example in which allosteric regulation of an enzyme activity is achieved through the formation of quaternary structure. Here, we report a 1.7 A resolution structure of Kaposi's sarcoma-associated herpesvirus protease in complex with a hexapeptide transition state analogue that stabilizes the dimeric state of the enzyme. Extended substrate binding sites are induced upon peptide binding. In particular, 104 A2 of surface are buried in the newly formed S4 pocket when tyrosine binds at this site. The peptide inhibitor also induces a rearrangement of residues that stabilizes the oxyanion hole and the dimer interface. Concomitant with the structural changes, an increase in catalytic efficiency of the enzyme results upon extended substrate binding. A nearly 20-fold increase in kcat/KM results upon extending the peptide substrate from a tetrapeptide to a hexapeptide exclusively due to a KM effect. This suggests that the mechanism by which herpesvirus proteases achieve their high specificity is by using extended substrates to modulate both the structure and activity of the enzyme.
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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.