ArticleOpen biology2016
Allosteric inhibition of Aurora-A kinase by a synthetic vNAR domain.
Article in Open biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Light-induced spindle assembly through Aurora A clustering.EMBO reports · 2026Article
- Structural characterization and inhibition of the interaction between ch-TOG and TACC3.The Journal of cell biology · 2025Article
- Research progress on the relationship between AURKA and tumorigenesis: the neglected nuclear function of AURKA.Annals of medicine · 2024Review
- CEP192 localises mitotic Aurora-A activity by priming its interaction with TPX2.The EMBO journal · 2024Article
- Review
- The role of Aurora kinase A in hepatocellular carcinoma: Unveiling the intriguing functions of a key but still underexplored factor in liver cancer.Cell proliferation · 2024Review
- vNARs as Neutralizing Intracellular Therapeutic Agents: Glioblastoma as a Target.Antibodies (Basel, Switzerland) · 2024Review
- A nanobody inhibitor of Fascin-1 actin-bundling activity and filopodia formation.Open biology · 2024Article
- Shark IgNAR: The Next Broad Application Antibody in Clinical Diagnoses and Tumor Therapies?Marine drugs · 2023Review
- Chimeric Peptides fromToxins · 2023Article
- Exploring the Conformational Landscape and Stability of Aurora A Using Ion-Mobility Mass Spectrometry and Molecular Modeling.Journal of the American Society for Mass Spectrometry · 2022Article
- Overview, Generation, and Significance of Variable New Antigen Receptors (VNARs) as a Platform for Drug and Diagnostic Development.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Nuclear localisation of Aurora-A: its regulation and significance for Aurora-A functions in cancer.Oncogene · 2021Review
- Ancient species offers contemporary therapeutics: an update on shark VAntibody therapeutics · 2020Review
- Allosteric modulation of a human protein kinase with monobodies.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Synthetic libraries of shark vNAR domains with different cysteine numbers within the CDR3.PloS one · 2019Article
- Quantitative conformational profiling of kinase inhibitors reveals origins of selectivity for Aurora kinase activation states.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The multifaceted allosteric regulation of Aurora kinase A.The Biochemical journal · 2018Review
- Article
- Mitotic spindle association of TACC3 requires Aurora-A-dependent stabilization of a cryptic α-helix.The EMBO journal · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The vast majority of clinically approved protein kinase inhibitors target the ATP-binding pocket directly. Consequently, many inhibitors have broad selectivity profiles and most have significant off-target effects. Allosteric inhibitors are generally more selective, but are difficult to identify because allosteric binding sites are often unknown or poorly characterized. Aurora-A is activated through binding of TPX2 to an allosteric site on the kinase catalytic domain, and this knowledge could be exploited to generate an inhibitor. Here, we generated an allosteric inhibitor of Aurora-A kinase based on a synthetic, vNAR single domain scaffold, vNAR-D01. Biochemical studies and a crystal structure of the Aurora-A/vNAR-D01 complex show that the vNAR domain overlaps with the TPX2 binding site. In contrast with the binding of TPX2, which stabilizes an active conformation of the kinase, binding of the vNAR domain stabilizes an inactive conformation, in which the αC-helix is distorted, the canonical Lys-Glu salt bridge is broken and the regulatory (R-) spine is disrupted by an additional hydrophobic side chain from the activation loop. These studies illustrate how single domain antibodies can be used to characterize the regulatory mechanisms of kinases and provide a rational basis for structure-guided design of allosteric Aurora-A kinase inhibitors.
Indexed as
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What OpenQuestion 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 OpenQuestion graph.