ArticleNature chemical biology2017
A water-mediated allosteric network governs activation of Aurora kinase A.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 64 citations in OpenAlex.
- Molecular basis for the activation of Aurora A and Plk1 kinases during mitotic entry.The EMBO journal · 2026Article
- Deep GIST: Deep Learning Models for Predicting the Distribution of Hydration Thermodynamics around Proteins.Journal of chemical information and modeling · 2026Article
- Aurora A binds to the transactivation domain of c-Myc and recognizes the phosphorylated N-terminal degron motif.The Biochemical journal · 2025Article
- CEP192 localises mitotic Aurora-A activity by priming its interaction with TPX2.The EMBO journal · 2024Article
- Exploring the conformational landscape of protein kinases.Current opinion in structural biology · 2024Review
- Exploring the conformational landscapes of protein kinases: perspectives from FRET and DEER.Biochemical Society transactions · 2024Review
- From functional plasticity of two diterpene synthases (IrTPS2/IrKSL3a) to enzyme evolution.ACS catalysis · 2024Article
- A biophysical framework for double-drugging kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Structural basis for CEP192-mediated regulation of centrosomal AURKA.Science advances · 2023Article
- A biophysical framework for double-drugging kinases.bioRxiv : the preprint server for biology · 2023Article
- Aurora Kinase A Regulation by Cysteine Oxidative Modification.Antioxidants (Basel, Switzerland) · 2023Review
- Protein kinase C: release from quarantine by mTORC2.Trends in biochemical sciences · 2022Review
- Modulation of P2X4 pore closure by magnesium, potassium, and ATP.Biophysical journal · 2022Article
- Structure-mechanics statistical learning uncovers mechanical relay in proteins.Chemical science · 2022Article
- Regulatory spine RS3 residue of protein kinases: a lipophilic bystander or a decisive element in the small-molecule kinase inhibitor binding?Biochemical Society transactions · 2022Article
- Phosphorylation-Dependent Regulation of WNT/Beta-Catenin Signaling.Frontiers in oncology · 2022Review
- Dynamic equilibria in protein kinases.Current opinion in structural biology · 2021Review
- Trends in kinase drug discovery: targets, indications and inhibitor design.Nature reviews. Drug discovery · 2021Review
- Bora phosphorylation substitutes in trans for T-loop phosphorylation in Aurora A to promote mitotic entry.Nature communications · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The catalytic activity of many protein kinases is controlled by conformational changes of a conserved Asp-Phe-Gly (DFG) motif. We used an infrared probe to track the DFG motif of the mitotic kinase Aurora A (AurA) and found that allosteric activation by the spindle-associated protein Tpx2 involves an equilibrium shift toward the active DFG-in state. Förster resonance energy transfer experiments show that the activation loop undergoes a nanometer-scale movement that is tightly coupled to the DFG equilibrium. Tpx2 further activates AurA by stabilizing a water-mediated allosteric network that links the C-helix to the active site through an unusual polar residue in the regulatory spine. The polar spine residue and water network of AurA are essential for phosphorylation-driven activation, but an alternative form of the water network found in related kinases can support Tpx2-driven activation, suggesting that variations in the water-mediated hydrogen bond network mediate regulatory diversification in protein kinases.
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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.