ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
Crystal structure of ED-Eya2: insight into dual roles as a protein tyrosine phosphatase and a transcription factor.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Rational Design of Novel Allosteric EYA2 Inhibitors as Potential Therapeutics for Multiple Brain Cancers.ChemMedChem · 2024Article
- All eyes on Eya: A unique transcriptional co-activator and phosphatase in cancer.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- Using Xenopus to discover new candidate genes involved in BOR and other congenital hearing loss syndromes.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2024Review
- A Benzarone Derivative Inhibits EYA to Suppress Tumor Growth in SHH Medulloblastoma.Cancer research · 2024Article
- In Vitro Phosphatase Assays for the Eya2 Tyrosine Phosphatase.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Stem Cell Bioengineering with Bioportides: Inhibition of Planarian Head Regeneration with Peptide Mimetics of Eyes Absent Proteins.Pharmaceutics · 2023Article
- Structure-activity relationship studies of allosteric inhibitors of EYA2 tyrosine phosphatase.Protein science : a publication of the Protein Society · 2022Article
- The Eyes Absent Proteins: Unusual HAD Family Tyrosine Phosphatases.International journal of molecular sciences · 2021Review
- Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery.International journal of molecular sciences · 2020Review
- Functional analysis of Rossmann-like domains reveals convergent evolution of topology and reaction pathways.PLoS computational biology · 2019Article
- Structural and Functional Analyses of an Allosteric EYA2 Phosphatase Inhibitor That Has On-Target Effects in Human Lung Cancer Cells.Molecular cancer therapeutics · 2019Article
- Inhibitors of Serine/Threonine Protein Phosphatases: Biochemical and Structural Studies Provide Insight for Further Development.Current medicinal chemistry · 2019Review
- Aberrant methylation of EYA4 promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma.Cancer science · 2018Article
- TheThe Journal of biological chemistry · 2018Article
- The Eya phosphatase: Its unique role in cancer.The international journal of biochemistry & cell biology · 2018Review
- WDR1 is a novel EYA3 substrate and its dephosphorylation induces modifications of the cellular actin cytoskeleton.Scientific reports · 2018Article
- The retinal determination gene network: from developmental regulator to cancer therapeutic target.Oncotarget · 2016Review
- Multiple Functions of the Eya Phosphotyrosine Phosphatase.Molecular and cellular biology · 2015Review
- The SIX1-EYA transcriptional complex as a therapeutic target in cancer.Expert opinion on therapeutic targets · 2015Review
- Allosteric inhibitors of the Eya2 phosphatase are selective and inhibit Eya2-mediated cell migration.The Journal of biological chemistry · 2014Article
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8 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Eya proteins are transcription factors that play pivotal roles in organ formation during development by mediating interactions between Sine Oculis (SO) and Dachshund (DAC). Remarkably, the transcriptional activity of Eya proteins is regulated by a dephosphorylating activity within its Eya domain (ED). However, the molecular basis for the link between catalytic and transcriptional activities remains unclear. Here we report the first description of the crystal structure of the ED of human Eya2 (ED-Eya2), determined at 2.4-A resolution. In stark contrast to other members of the haloacid dehalogenase (HAD) family to which ED-Eya2 belongs, the helix-bundle motif (HBM) is elongated along the back of the catalytic site. This not only results in a structure that accommodates large protein substrates but also positions the catalytic and the SO-interacting sites on opposite faces, which suggests that SO binding is not directly affected by catalytic function. Based on the observation that the DAC-binding site is located between the catalytic core and SO binding sites within ED-Eya2, we propose that catalytic activity can be translated to SO binding through DAC, which acts as a transcriptional switch. We also captured at two stages of reaction cycles-acyl-phosphate intermediate and transition state of hydrolysis step, which provided a detailed view of reaction mechanism. The ED-Eya2 structure defined here serves as a model for other members of the Eya family and provides a framework for understanding the role of Eya phosphatase mutations in disease.
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