ArticleACS chemical biology2013
Inhibitors of difficult protein-protein interactions identified by high-throughput screening of multiprotein complexes.
Article in ACS chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- Peptide-based molecules for the disruption of bacterial Hsp70 chaperones.Current opinion in chemical biology · 2023Review
- An allosteric inhibitor of bacterial Hsp70 chaperone potentiates antibiotics and mitigates resistance.Cell chemical biology · 2022Article
- Functional Effects of ARV-1502 Analogs Against Bacterial Hsp70 and Implications for Antimicrobial Activity.Frontiers in chemistry · 2022Article
- Binding Characterization of Cyclic Peptide Ligands to Target Proteins and Chemical Epitopes Using ELISA and Fluorescence Polarization Assays.Methods in molecular biology (Clifton, N.J.) · 2022Article
- 3,7-Dihydroxytropolones Inhibit Initiation of Hepatitis B Virus Minus-Strand DNA Synthesis.Molecules (Basel, Switzerland) · 2020Article
- Selective Modulation of Dynamic Protein Complexes.Cell chemical biology · 2020Review
- Targeting Difficult Protein-Protein Interactions with Plain and General Computational Approaches.Molecules (Basel, Switzerland) · 2018Review
- Protein-Protein Interactions in the Molecular Chaperone Network.Accounts of chemical research · 2018Review
- High-throughput screen for inhibitors of protein-protein interactions in a reconstituted heat shock protein 70 (Hsp70) complex.The Journal of biological chemistry · 2018Article
- Backbone and methyl resonance assignments of the 42 kDa human Hsc70 nucleotide binding domain in the ADP state.Biomolecular NMR assignments · 2017Article
- From Fuzzy to Function: The New Frontier of Protein-Protein Interactions.Accounts of chemical research · 2017Article
- The remarkable multivalency of the Hsp70 chaperones.Cell stress & chaperones · 2017Review
- Personalized and targeted therapy of esophageal squamous cell carcinoma: an update.Annals of the New York Academy of Sciences · 2016Review
- Non-canonical Interactions between Heat Shock Cognate Protein 70 (Hsc70) and Bcl2-associated Anthanogene (BAG) Co-Chaperones Are Important for Client Release.The Journal of biological chemistry · 2016Article
- Model systems of protein-misfolding diseases reveal chaperone modifiers of proteotoxicity.Disease models & mechanisms · 2016Review
- Dynamical Structures of Hsp70 and Hsp70-Hsp40 Complexes.Structure (London, England : 1993) · 2016Review
- Motif mediated protein-protein interactions as drug targets.Cell communication and signaling : CCS · 2016Review
- Targeting transcription is no longer a quixotic quest.Nature chemical biology · 2015Article
- The Chemical Biology of Molecular Chaperones--Implications for Modulation of Proteostasis.Journal of molecular biology · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Protein-protein interactions (PPIs) are important in all aspects of cellular function, and there is interest in finding inhibitors of these contacts. However, PPIs with weak affinities and/or large interfaces have traditionally been more resistant to the discovery of inhibitors, partly because it is more challenging to develop high-throughput screening (HTS) methods that permit direct measurements of these physical interactions. Here, we explored whether the functional consequences of a weak PPI might be used as a surrogate for binding. As a model, we used the bacterial ATPase DnaK and its partners DnaJ and GrpE. Both DnaJ and GrpE bind DnaK and catalytically accelerate its ATP cycling, so we used stimulated nucleotide turnover to indirectly report on these PPIs. In pilot screens, we identified compounds that block activation of DnaK by either DnaJ or GrpE. Interestingly, at least one of these molecules blocked binding of DnaK to DnaJ, while another compound disrupted allostery between DnaK and GrpE without altering the physical interaction. These findings suggest that the activity of a reconstituted multiprotein complex might be used in some cases to identify allosteric inhibitors of challenging PPIs.
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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.