ArticleeLife2018
Dynamics of human protein kinase Aurora A linked to drug selectivity.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed.
- Single-molecule kinetic exploration of functional sub-states in an evolving phosphotriesterase.Nature communications · 2026Article
- The N-Myc MB0-MBI region interacts specifically and dynamically with the N-lobe of Aurora kinase A.Nature communications · 2026Article
- Mechanism and application of thiol-disulfide redox biosensors with a fluorescence-lifetime readout.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CEP192 localises mitotic Aurora-A activity by priming its interaction with TPX2.The EMBO journal · 2024Article
- Novel meriolin derivatives potently inhibit cell cycle progression and transcription in leukemia and lymphoma cells via inhibition of cyclin-dependent kinases (CDKs).Cell death discovery · 2024Article
- A biophysical framework for double-drugging kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Analysis of Predicted Amino Acid Sequences of Diatom Microtubule Center Components.International journal of molecular sciences · 2023Article
- Article
- A biophysical framework for double-drugging kinases.bioRxiv : the preprint server for biology · 2023Article
- Protein Flexibility and Dissociation Pathway Differentiation Can Explain Onset of Resistance Mutations in Kinases.Angewandte Chemie (International ed. in English) · 2022Article
- Enhanced sampling without borders: on global biasing functions and how to reweight them.Physical chemistry chemical physics : PCCP · 2022Review
- Dynamics of protein kinases and pseudokinases by HDX-MS.Methods in enzymology · 2022Article
- Energy penalties enhance flexible receptor docking in a model cavity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Conformational interconversion of MLKL and disengagement from RIPK3 precede cell death by necroptosis.Nature communications · 2021Article
- Disorder in a two-domain neuronal CaCellular and molecular life sciences : CMLS · 2021Article
- Grating-coupled interferometry reveals binding kinetics and affinities of Ni ions to genetically engineered protein layers.Scientific reports · 2020Article
- The role of NMR in leveraging dynamics and entropy in drug design.Journal of biomolecular NMR · 2020Article
- Cooperativity Between Orthosteric Inhibitors and Allosteric Inhibitor 8-Anilino-1-Naphthalene Sulfonic Acid (ANS) in Cyclin-Dependent Kinase 2.ACS chemical biology · 2020Article
- Monobodies as enabling tools for structural and mechanistic biology.Current opinion in structural biology · 2020Review
- Covalent Aurora A regulation by the metabolic integrator coenzyme A.Redox biology · 2020Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Protein kinases are major drug targets, but the development of highly-selective inhibitors has been challenging due to the similarity of their active sites. The observation of distinct structural states of the fully-conserved Asp-Phe-Gly (DFG) loop has put the concept of conformational selection for the DFG-state at the center of kinase drug discovery. Recently, it was shown that Gleevec selectivity for the Tyr-kinase Abl was instead rooted in conformational changes after drug binding. Here, we investigate whether protein dynamics after binding is a more general paradigm for drug selectivity by characterizing the binding of several approved drugs to the Ser/Thr-kinase Aurora A. Using a combination of biophysical techniques, we propose a universal drug-binding mechanism, that rationalizes selectivity, affinity and long on-target residence time for kinase inhibitors. These new concepts, where protein dynamics in the drug-bound state plays the crucial role, can be applied to inhibitor design of targets outside the kinome.
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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.