ArticleProceedings of the National Academy of Sciences of the United States of America2014
Dissecting allosteric effects of activator-coactivator complexes using a covalent small molecule ligand.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 36 citations in OpenAlex.
- Fluorine-Thiol Displacement Stapling on the Disordered αSynlett : accounts and rapid communications in synthetic organic chemistry · 2025Article
- Inhibition of CREB Binding and Function with a Dual-Targeting Ligand.Biochemistry · 2024Article
- Allostery in the dynamic coactivator domain KIX occurs through minor conformational micro-states.PLoS computational biology · 2022Article
- Targeting protein-protein interaction interfaces in COVID-19 drug discovery.Computational and structural biotechnology journal · 2021Review
- 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
- Recent advances in the development of protein-protein interactions modulators: mechanisms and clinical trials.Signal transduction and targeted therapy · 2020Review
- Integrated Computational Approaches and Tools forAllosteric Drug Discovery.International journal of molecular sciences · 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
- Structural basis for cooperative regulation of KIX-mediated transcription pathways by the HTLV-1 HBZ activation domain.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Covalent Chemical Cochaperones of the p300/CBP GACKIX Domain.Chembiochem : a European journal of chemical biology · 2018Article
- Conservation of coactivator engagement mechanism enables small-molecule allosteric modulators.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Expanding the Paradigm: Intrinsically Disordered Proteins and Allosteric Regulation.Journal of molecular biology · 2018Review
- Modulating the masters: chemical tools to dissect CBP and p300 function.Current opinion in chemical biology · 2018Review
- Inhibitors of protein-protein interactions (PPIs): an analysis of scaffold choices and buried surface area.Current opinion in chemical biology · 2018Review
- From Fuzzy to Function: The New Frontier of Protein-Protein Interactions.Accounts of chemical research · 2017Article
- Systematic Targeting of Protein-Protein Interactions.Trends in pharmacological sciences · 2016Review
- Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein.Scientific reports · 2016Article
- The 9aaTAD Transactivation Domains: From Gal4 to p53.PloS one · 2016Article
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
Allosteric binding events play a critical role in the formation and stability of transcriptional activator-coactivator complexes, perhaps in part due to the often intrinsically disordered nature of one or more of the constituent partners. The kinase-inducible domain interacting (KIX) domain of the master coactivator CREB binding protein/p300 is a conformationally dynamic domain that complexes with transcriptional activators at two discrete binding sites in allosteric communication. The complexation of KIX with the transcriptional activation domain of mixed-lineage leukemia protein leads to an enhancement of binding by the activation domain of CREB (phosphorylated kinase-inducible domain of CREB) to the second site. A transient kinetic analysis of the ternary complex formation aided by small molecule ligands that induce positive or negative cooperative binding reveals that positive cooperativity is largely governed by stabilization of the bound complex as indicated by a decrease in koff. Thus, this suggests the increased binding affinity for the second ligand is not due to an allosteric creation of a more favorable binding interface by the first ligand. This is consistent with data from us and from others indicating that the on rates of conformationally dynamic proteins approach the limits of diffusion. In contrast, negative cooperativity is manifested by alterations in both kon and koff, suggesting stabilization of the binary complex.
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.