ArticleNature structural & molecular biology2017
Atomic view of the energy landscape in the allosteric regulation of Abl kinase.
Article in Nature structural & molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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.
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.
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Who cites it
47 citing papers in PubMed, 65 citations in OpenAlex.
- Decoding the allosteric grammar of protein kinases: A dual-stream framework integrating protein language models and energy landscape frustration analysis.Protein science : a publication of the Protein Society · 2026Article
- Dual functional genomics reveals a broad and convergent landscape of asciminib resistance in BCR::ABL1.Genome medicine · 2026Article
- Constraining regulatory domain dynamics of the Src kinase Fgr increases ATP-site inhibitor sensitivity and impairs bone marrow engraftment.Cell reports · 2026Article
- The Discovery of Abl Kinase ATPase Activity and Its Implications in the Development of Straightforward Assays.ACS omega · 2025Article
- Effect of Electric Fields on the Mechanical Mechanism of Regorafenib-VEGFR2 Interaction to Enhance Inhibition of Hepatocellular Carcinoma.Biomolecules · 2025Article
- Probing Functional Allosteric States and Conformational Ensembles of the Allosteric Protein Kinase States and Mutants: Atomistic Modeling and Comparative Analysis of AlphaFold2, OmegaFold, and AlphaFlow Approaches and Adaptations.The journal of physical chemistry. B · 2024Article
- Exploring the conformational landscape of protein kinases.Current opinion in structural biology · 2024Review
- Predicting Mutation-Induced Allosteric Changes in Structures and Conformational Ensembles of the ABL Kinase Using AlphaFold2 Adaptations with Alanine Sequence Scanning.International journal of molecular sciences · 2024Article
- Overcoming clinical BCR-ABL1 compound mutant resistance with combined ponatinib and asciminib therapy.Cancer cell · 2024Article
- Integration of a Randomized Sequence Scanning Approach in AlphaFold2 and Local Frustration Profiling of Conformational States Enable Interpretable Atomistic Characterization of Conformational Ensembles and Detection of Hidden Allosteric States in the ABL1 Protein Kinase.Journal of chemical theory and computation · 2024Article
- Prophylactic treatment with the c-Abl inhibitor, neurotinib, diminishes neuronal damage and the convulsive state in pilocarpine-induced mice.Cell reports · 2024Article
- Protein conformational ensembles in function: roles and mechanisms.RSC chemical biology · 2023Review
- Article
- A biophysical framework for double-drugging kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A biophysical framework for double-drugging kinases.bioRxiv : the preprint server for biology · 2023Article
- The "violin model": Looking at community networks for dynamic allostery.The Journal of chemical physics · 2023Review
- 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
- Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs.Journal of molecular biology · 2022Review
- Validation of an Allosteric Binding Site of Src Kinase Identified by Unbiased Ligand Binding Simulations.Journal of molecular biology · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The activity of protein kinases is often regulated in an intramolecular fashion by signaling domains, which feature several phosphorylation or protein-docking sites. How kinases integrate such distinct binding and signaling events to regulate their activities is unclear, especially in quantitative terms. We used NMR spectroscopy to show how structural elements within the Abl regulatory module (RM) synergistically generate a multilayered allosteric mechanism that enables Abl kinase to function as a finely tuned switch. We dissected the structure and energetics of the regulatory mechanism to precisely measure the effects of various activating or inhibiting stimuli on Abl kinase activity. The data provide a mechanistic basis explaining genetic observations and reveal a previously unknown activator region within Abl. Our findings show that drug-resistance mutations in the Abl RM exert their allosteric effect by promoting the activated state of Abl and not by decreasing the drug affinity for the kinase.
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What Socratic 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 Socratic graph.