ArticleNature communications2015
A dynamically coupled allosteric network underlies binding cooperativity in Src kinase.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
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Who cites it
76 citing papers in PubMed, 123 citations in OpenAlex.
- Residue Interaction Network Reveals Allosteric Pathways Linking Orthosteric and Intracellular Sites in Class A GPCRs.Journal of chemical information and modeling · 2026Article
- Mapping of dynamic allostery within p38 alpha kinase via network analyses and NMR spectroscopy.Nature communications · 2026Article
- Adaptive Normal Mode Sampling (aMDeNM) Enhances Exploration of Protein Conformational Space and Reveals the Functional Role of Frequency Coupling.Journal of chemical theory and computation · 2026Article
- Substrate-derived peptides for selective covalent inhibition of protein tyrosine kinases.bioRxiv : the preprint server for biology · 2026Article
- Lipid Pocket Binders Impose Allosteric Changes of Protein Dynamics Around the Active Site of the Protein Kinase p38α.Angewandte Chemie (International ed. in English) · 2026Article
- The stress-activated kinase p38 mediates non-canonical activation of Src and tyrosine phosphorylation of the adapter protein TAB1.The Journal of biological chemistry · 2026Article
- Defining the Active Conformation of Typical Protein Kinase Domains from Substrate-Bound PDB Structures Enables Active-State AlphaFold2 Models for All 437 Human Catalytic Protein Kinases.bioRxiv : the preprint server for biology · 2026Article
- The allosteric landscape of the Src kinase.Science advances · 2026Article
- Allosteric binding cooperativity in kinases signaling, signalopathies, and drug development.Current opinion in structural biology · 2025Review
- Allosteric Coupling in Full-Length Lyn Kinase Revealed by Molecular Dynamics and Network Analysis.International journal of molecular sciences · 2025Article
- 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
- Article
- Genetically encoded bioorthogonal tryptophan decaging in living cells.Nature chemistry · 2024Article
- Allo-targeting of the kinase domain: Insights from in silico studies and comparison with experiments.Current opinion in structural biology · 2024Review
- Comparative Atomistic Insights on Apo and ATP-I1171N/S/T in Nonsmall-Cell Lung Cancer.ACS omega · 2023Article
- Programming conformational cooperativity to regulate allosteric protein-oligonucleotide signal transduction.Nature communications · 2023Article
- Conformational changes in protein kinase A along its activation cycle are rooted in the folding energetics of cyclic-nucleotide binding domains.The Journal of biological chemistry · 2023Article
- Article
- Allosteric regulation and inhibition of protein kinases.Biochemical Society transactions · 2023Review
- Probing conformational landscapes and mechanisms of allosteric communication in the functional states of the ABL kinase domain using multiscale simulations and network-based mutational profiling of allosteric residue potentials.The Journal of chemical physics · 2022Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Protein tyrosine kinases are attractive drug targets because many human diseases are associated with the deregulation of kinase activity. However, how the catalytic kinase domain integrates different signals and switches from an active to an inactive conformation remains incompletely understood. Here we identify an allosteric network of dynamically coupled amino acids in Src kinase that connects regulatory sites to the ATP- and substrate-binding sites. Surprisingly, reactants (ATP and peptide substrates) bind with negative cooperativity to Src kinase while products (ADP and phosphopeptide) bind with positive cooperativity. We confirm the molecular details of the signal relay through the allosteric network by biochemical studies. Experiments on two additional protein tyrosine kinases indicate that the allosteric network may be largely conserved among these enzymes. Our work provides new insights into the regulation of protein tyrosine kinases and establishes a potential conduit by which resistance mutations to ATP-competitive kinase inhibitors can affect their activity.
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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.