ArticleComputational and structural biotechnology journal2022
Allosteric regulation of autoinhibition and activation of c-Abl.
Article in Computational and structural biotechnology journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 31 citations in OpenAlex.
- Bend and Snap: Computationally Exploring the Helix Bias for Classifying Abl Kinase Allosteric Modulators.Journal of chemical information and modeling · 2026Article
- Article
- Discovery of a Novel 4,5-Dihydro-1Biomedicines · 2026Article
- Allosteric drugs in biomolecular condensates: ways forward.Drug discovery today · 2026Review
- Allostery in Biomolecular Condensates.Journal of molecular biology · 2026Review
- Expression, purification, and crystallization of recombinant human ABL-1 kinase for X-ray crystallography.Turkish journal of chemistry · 2026Article
- The structural heterogeneity of AKT autoinhibition.Protein science : a publication of the Protein Society · 2026Article
- ERK Allosteric Activation: The Importance of Two Ordered Phosphorylation Events.Journal of molecular biology · 2025Article
- Distinct Allosteric Networks in CDK4 and CDK6 in the Cell Cycle and in Drug Resistance.Journal of molecular biology · 2025Article
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- Drug resistance and tumor heterogeneity: cells and ensembles.Biophysical reviews · 2025Review
- Structure and Dynamics of the ABL1 Tyrosine Kinase and Its Important Role in Chronic Myeloid Leukemia.Archiv der Pharmazie · 2025Review
- Molecular principles underlying aggressive cancers.Signal transduction and targeted therapy · 2025Review
- Allosteric modulation of NF1 GAP: Differential distributions of catalytically competent populations in loss-of-function and gain-of-function mutants.Protein science : a publication of the Protein Society · 2025Article
- mTOR Variants Activation Discovers PI3K-like Cryptic Pocket, Expanding Allosteric, Mutant-Selective Inhibitor Designs.Journal of chemical information and modeling · 2025Article
- Anticancer Target Combinations: Network-Informed Signaling-Based Approach to Discovery.bioRxiv : the preprint server for biology · 2024Article
- Capturing Autoinhibited PDK1 Reveals the Linker's Regulatory Role, Informing Innovative Inhibitor Design.Journal of chemical information and modeling · 2024Article
- The value of protein allostery in rational anticancer drug design: an update.Expert opinion on drug discovery · 2024Review
- Slower CDK4 and faster CDK2 activation in the cell cycle.Structure (London, England : 1993) · 2024Article
- CDK2 and CDK4: Cell Cycle Functions Evolve Distinct, Catalysis-Competent Conformations, Offering Drug Targets.JACS Au · 2024Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
c-Abl, a non-receptor tyrosine kinase, regulates cell growth and survival in healthy cells and causes chronic myeloid leukemia (CML) when fused by Bcr. Its activity is blocked in the assembled inactive state, where the SH3 and SH2 domains dock into the kinase domain, reducing its conformational flexibility, resulting in the autoinhibited state. It is active in an extended 'open' conformation. Allostery governs the transitions between the autoinhibited and active states. Even though experiments revealed the structural hallmarks of the two states, a detailed grasp of the determinants of c-Abl autoinhibition and activation at the atomic level, which may help innovative drug discovery, is still lacking. Here, using extensive molecular dynamics simulations, we decipher exactly how these determinants regulate it. Our simulations confirm and extend experimental data that the myristoyl group serves as the switch for c-Abl inhibition/activation. Its dissociation from the kinase domain promotes the SH2-SH3 release, initiating c-Abl activation. We show that the precise SH2/
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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 Socratic graph.