ArticleJournal of the American Chemical Society2013
Ordering a dynamic protein via a small-molecule stabilizer.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed.
- From Concepts to Inhibitors: A Blueprint for Targeting Protein-Protein Interactions.Chemical reviews · 2025Review
- Article
- FITA-Containing 2,4-Dinitrophenyl Alkylthioether-Based Probe for Detection and Imaging of GSH.Sensors (Basel, Switzerland) · 2024Article
- Inhibition of CREB Binding and Function with a Dual-Targeting Ligand.Biochemistry · 2024Article
- Garcinolic Acid Distinguishes Between GACKIX Domains and Modulates Interaction Networks.Chembiochem : a European journal of chemical biology · 2023Article
- Minimum information guidelines for experiments structurally characterizing intrinsically disordered protein regions.Nature methods · 2023Review
- Reversible Dual-Covalent Molecular Locking of the 14-3-3/ERRγ Protein-Protein Interaction as a Molecular Glue Drug Discovery Approach.Journal of the American Chemical Society · 2023Article
- Towards identification of protein-protein interaction stabilizersRSC chemical biology · 2022Article
- Allostery in the dynamic coactivator domain KIX occurs through minor conformational micro-states.PLoS computational biology · 2022Article
- Cryo-EM, Protein Engineering, and Simulation Enable the Development of Peptide Therapeutics against Acute Myeloid Leukemia.ACS central science · 2022Article
- Review
- Advances in targeting 'undruggable' transcription factors with small molecules.Nature reviews. Drug discovery · 2021Review
- Identification of β-strand mediated protein-protein interaction inhibitors using ligand-directed fragment ligation.Chemical science · 2021Article
- Visualizing and trapping transient oligomers in amyloid assembly pathways.Biophysical chemistry · 2021Review
- Modulation of Amyloidogenic Protein Self-Assembly Using Tethered Small Molecules.Journal of the American Chemical Society · 2020Article
- Unexpected specificity within dynamic transcriptional protein-protein complexes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Revisiting allostery in CREB-binding protein (CBP) using residue-based interaction energy.Journal of computer-aided molecular design · 2020Article
- Selective Modulation of Dynamic Protein Complexes.Cell chemical biology · 2020Review
- Structural and mechanistic insights into the interaction of the circadian transcription factor BMAL1 with the KIX domain of the CREB-binding protein.The Journal of biological chemistry · 2019Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
Like many coactivators, the GACKIX domain of the master coactivator CBP/p300 recognizes transcriptional activators of diverse sequence composition via dynamic binding surfaces. The conformational dynamics of GACKIX that underlie its function also render it especially challenging for structural characterization. We have found that the ligand discovery strategy of Tethering is an effective method for identifying small-molecule fragments that stabilize the GACKIX domain, enabling for the first time the crystallographic characterization of this important motif. The 2.0 Å resolution structure of GACKIX complexed to a small molecule was further analyzed by molecular dynamics simulations, which revealed the importance of specific side-chain motions that remodel the activator binding site in order to accommodate binding partners of distinct sequence and size. More broadly, these results suggest that Tethering can be a powerful strategy for identifying small-molecule stabilizers of conformationally malleable proteins, thus facilitating their structural characterization and accelerating the discovery of small-molecule modulators.
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.