ArticleNature chemical biology2021
Allostery governs Cdk2 activation and differential recognition of CDK inhibitors.
Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 71 citations in OpenAlex.
- The non-canonical CDK2 activator SPY1 uses separable mechanisms to activate phosphorylated and unphosphorylated CDK2.The Biochemical journal · 2026Article
- Enhanced Sampling of Protein Conformations in AlphaFold3 with Repulsive Bias in the Diffusion Generative Model.JACS Au · 2026Article
- CDK4/6 Inhibitors for Breast Cancer Therapy-A Review of Clinical Trials, Structural and Computational Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- 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
- PROTACs for Collateral Degradation: Is It Time to Back Up the Bus?ACS medicinal chemistry letters · 2026Review
- DINC-ensemble: A web server for docking large ligands incrementally to an ensemble of receptor conformations.Journal of molecular biology · 2025Article
- Tyrosine-Mediated Static and Dynamic Quenching of a Receptor Tyrosine Kinase Biosensor Reveals Inhibitor Binding Modes and Kinase Conformations.ACS chemical biology · 2025Article
- The filopodial myosin DdMyo7 is a slow, calcium-regulated motor.The Journal of biological chemistry · 2025Article
- Targeting cyclin-dependent kinase 2 (CDK2) interactions with cyclins and Speedy 1 (Spy1) for cancer and male contraception.Future medicinal chemistry · 2025Review
- Emerging opportunities to treat drug-resistant breast cancer: Discovery of novel small-molecule inhibitors against different targets.Frontiers in pharmacology · 2025Review
- CDK2 Allosteric Modulators: The New Route in the Design of New Drugs as Anticancer and Non-hormonal Contraceptives.Current medicinal chemistry · 2025Review
- Latent allosteric control of protein interactions by ATP-competitive kinase inhibitors.Current opinion in structural biology · 2024Review
- Genomic Discovery and Structure-Activity Exploration of a Novel Family of Enzyme-Activated Covalent Cyclin-Dependent Kinase Inhibitors.Journal of medicinal chemistry · 2024Article
- Slower CDK4 and faster CDK2 activation in the cell cycle.Structure (London, England : 1993) · 2024Article
- Exploring the conformational landscapes of protein kinases: perspectives from FRET and DEER.Biochemical Society transactions · 2024Review
- CDK2 and CDK4: Cell Cycle Functions Evolve Distinct, Catalysis-Competent Conformations, Offering Drug Targets.JACS Au · 2024Article
- Allosteric coupling asymmetry mediates paradoxical activation of BRAF by type II inhibitors.eLife · 2024Article
- Activation Loop Plasticity and Active Site Coupling in the MAP Kinase, ERK2.Journal of molecular biology · 2023Article
- Development of allosteric and selective CDK2 inhibitors for contraception with negative cooperativity to cyclin binding.Nature communications · 2023Article
- Emerging maps of allosteric regulation in cellular networks.Current opinion in structural biology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Cyclin-dependent kinases (CDKs) are the master regulators of the eukaryotic cell cycle. To become activated, CDKs require both regulatory phosphorylation and binding of a cognate cyclin subunit. We studied the activation process of the G1/S kinase Cdk2 in solution and developed a thermodynamic model that describes the allosteric coupling between regulatory phosphorylation, cyclin binding and inhibitor binding. The results explain why monomeric Cdk2 lacks activity despite sampling an active-like state, reveal that regulatory phosphorylation enhances allosteric coupling with the cyclin subunit and show that this coupling underlies differential recognition of Cdk2 and Cdk4 inhibitors. We identify an allosteric hub that has diverged between Cdk2 and Cdk4 and show that this hub controls the strength of allosteric coupling. The altered allosteric wiring of Cdk4 leads to compromised activity toward generic peptide substrates and comparative specialization toward its primary substrate retinoblastoma (RB).
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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.