ArticleJournal of the American Chemical Society2017
Allosteric Inhibitors, Crystallography, and Comparative Analysis Reveal Network of Coordinated Movement across Human Herpesvirus Proteases.
Article in Journal of the American Chemical Society, 2017. 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
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
11 citing papers in PubMed, 14 citations in OpenAlex.
- Antibody reveals conformational latch regulating dimerization in β- and γ-herpesvirus proteases.Nature communications · 2026Article
- Antibody Reveals Conformational Latch Controlling Herpesvirus Proteases.bioRxiv : the preprint server for biology · 2025Article
- Inhibiting a dynamic viral protease by targeting a non-catalytic cysteine.Cell chemical biology · 2022Article
- Which Properties Allow Ligands to Open and Bind to the Transient Binding Pocket of Human Aldose Reductase?Biomolecules · 2021Article
- High throughput and quantitative enzymology in the genomic era.Current opinion in structural biology · 2021Review
- Recent Advances in Developing Treatments of Kaposi's Sarcoma Herpesvirus-Related Diseases.Viruses · 2021Review
- Structure-Based Analysis of Cryptic-Site Opening.Structure (London, England : 1993) · 2020Article
- Advances in methods for atomic resolution macromolecular structure determination.F1000Research · 2020Review
- Predicting allostery and microbial drug resistance with molecular simulations.Current opinion in structural biology · 2018Review
- Discovery of acylphloroglucinol-based meroterpenoid enantiomers as KSHV inhibitors fromRSC advances · 2018Article
- Cryptic binding sites on proteins: definition, detection, and druggability.Current opinion in chemical biology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Targeting of cryptic binding sites represents an attractive but underexplored approach to modulating protein function with small molecules. Using the dimeric protease (Pr) from Kaposi's sarcoma-associated herpesvirus (KSHV) as a model system, we sought to dissect a putative allosteric network linking a cryptic site at the dimerization interface to enzyme function. Five cryogenic X-ray structures were solved of the monomeric protease with allosteric inhibitors bound to the dimer interface site. Distinct coordinated movements captured by the allosteric inhibitors were also revealed as alternative states in room-temperature X-ray data and comparative analyses of other dimeric herpesvirus proteases. A two-step mechanism was elucidated through detailed kinetic analyses and suggests an enzyme isomerization model of inhibition. Finally, a representative allosteric inhibitor from this class was shown to be efficacious in a cellular model of viral infectivity. These studies reveal a coordinated dynamic network of atomic communication linking cryptic binding site occupancy and allosteric inactivation of KHSV Pr that can be exploited to target other members of this clinically relevant family of enzymes.
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.