ArticleScience advances2022
ATP-competitive inhibitors modulate the substrate binding cooperativity of a kinase by altering its conformational entropy.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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Who cites it
32 citing papers in PubMed.
- Multi-omics analysis reveals the mechanism of enhanced GABA production in Lactiplantibacillus plantarum JY7 under acoustic and thermal coupling.Ultrasonics sonochemistry · 2026Article
- Unraveling competitive protein interactions: A critical step toward improved production and therapeutics.Journal of advanced research · 2026Review
- Quantum Reactivity-Guided Optimization of ATP-Competitive Ligands through Multiscale Simulation.ACS physical chemistry Au · 2026Article
- A PKA-selective inhibitor captures an open but more ordered conformation of the PKA catalytic subunit.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- In silico analysis of PERK interactions with engineered alpha lactalbumin peptides using molecular dynamics simulations.Scientific reports · 2026Article
- Cyclin-E/A/CDK1/2 Kinetic Landscapes Drive Cell Cycle Phase-Specific Progression and Guide Cyclin-E Degradation Strategy.Journal of chemical information and modeling · 2026Article
- The Power of Protein Dynamics in Binding and Allostery.Biochemistry · 2026Review
- Conformation-programmed DNA computing.Science advances · 2026Article
- Chemical synthesis of novel aminopyrimidin-4-yl-1H-pyrazole derivatives as spleen tyrosine kinase (SYK) inhibitors.Scientific reports · 2026Article
- Phosphoinositide-dependent kinase 1 (PDK1) in cancer: molecular insights and therapeutic strategies.Frontiers in chemistry · 2026Review
- Crystallographic Ensembles Reveal the Structural Basis of Binding Entropy in SARS-CoV2 Macrodomain.bioRxiv : the preprint server for biology · 2025Article
- Allosteric binding cooperativity in kinases signaling, signalopathies, and drug development.Current opinion in structural biology · 2025Review
- Activity of Serpins in Context to Hydrophobic Interaction.Biomolecules · 2025Article
- Discriminating activating, deactivating and resistance variants in protein kinases.Genome medicine · 2025Article
- Exploring protein adenylyltransferase as a therapeutic target for combating ESKAPE pathogens in hospital-acquired infections.Molecular biology reports · 2025Review
- Local and distal changes in dynamics are caused by an L205R Cushing's syndrome mutant in PRKACA.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Advances in uncovering the mechanisms of macromolecular conformational entropy.Nature chemical biology · 2025Review
- Advances in pyrazolo[1,5-RSC advances · 2025Review
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Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
ATP-competitive inhibitors are currently the largest class of clinically approved drugs for protein kinases. By targeting the ATP-binding pocket, these compounds block the catalytic activity, preventing substrate phosphorylation. A problem with these drugs, however, is that inhibited kinases may still recognize and bind downstream substrates, acting as scaffolds or binding hubs for signaling partners. Here, using protein kinase A as a model system, we show that chemically different ATP-competitive inhibitors modulate the substrate binding cooperativity by tuning the conformational entropy of the kinase and shifting the populations of its conformationally excited states. Since we found that binding cooperativity and conformational entropy of the enzyme are correlated, we propose a new paradigm for the discovery of ATP-competitive inhibitors, which is based on their ability to modulate the allosteric coupling between nucleotide and substrate-binding sites.
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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.