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Open data
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Basic information
Entry | Database: PDB / ID: 8at9 | ||||||
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Title | Small molecule stabilizer for ERalpha and 14-3-3 (1080269) | ||||||
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![]() | STRUCTURAL PROTEIN / 14-3-3 / ERalpha / stabilization / covalent | ||||||
Function / homology | ![]() regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / regulation of branching involved in prostate gland morphogenesis / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / regulation of epidermal cell division / protein kinase C inhibitor activity / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis ...regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / regulation of branching involved in prostate gland morphogenesis / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / regulation of epidermal cell division / protein kinase C inhibitor activity / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / nuclear estrogen receptor activity / positive regulation of epidermal cell differentiation / epithelial cell proliferation involved in mammary gland duct elongation / keratinocyte development / epithelial cell development / keratinization / prostate epithelial cord elongation / negative regulation of smooth muscle cell apoptotic process / mammary gland branching involved in pregnancy / uterus development / vagina development / TFIIB-class transcription factor binding / Regulation of localization of FOXO transcription factors / androgen metabolic process / steroid hormone receptor signaling pathway / keratinocyte proliferation / phosphoserine residue binding / Activation of BAD and translocation to mitochondria / negative regulation of keratinocyte proliferation / mammary gland alveolus development / estrogen receptor signaling pathway / establishment of skin barrier / cellular response to estrogen stimulus / estrogen response element binding / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / : / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / nuclear receptor-mediated steroid hormone signaling pathway / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / negative regulation of stem cell proliferation / negative regulation of canonical NF-kappaB signal transduction / Nuclear signaling by ERBB4 / RNA polymerase II preinitiation complex assembly / RHO GTPases activate PKNs / protein localization to chromatin / 14-3-3 protein binding / protein kinase A signaling / protein sequestering activity / TBP-class protein binding / negative regulation of innate immune response / nitric-oxide synthase regulator activity / protein export from nucleus / steroid binding / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / ESR-mediated signaling / transcription corepressor binding / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / positive regulation of protein export from nucleus / release of cytochrome c from mitochondria / negative regulation of miRNA transcription / positive regulation of nitric-oxide synthase activity / stem cell proliferation / cellular response to estradiol stimulus / transcription coregulator binding / Translocation of SLC2A4 (GLUT4) to the plasma membrane / stem cell differentiation / nuclear estrogen receptor binding / TP53 Regulates Metabolic Genes / negative regulation of protein kinase activity / SUMOylation of intracellular receptors / euchromatin / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of DNA-binding transcription factor activity / beta-catenin binding / transcription coactivator binding / positive regulation of DNA-binding transcription factor activity / Nuclear Receptor transcription pathway / response to estrogen / Regulation of RUNX2 expression and activity / Constitutive Signaling by Aberrant PI3K in Cancer / nuclear receptor activity / male gonad development / intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of nitric oxide biosynthetic process / sequence-specific double-stranded DNA binding / positive regulation of fibroblast proliferation / Ovarian tumor domain proteases / PIP3 activates AKT signaling / response to estradiol / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / ATPase binding / fibroblast proliferation / regulation of inflammatory response / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / positive regulation of cell growth / DNA-binding transcription activator activity, RNA polymerase II-specific / Estrogen-dependent gene expression / transcription regulator complex / Extra-nuclear estrogen signaling Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Visser, E.J. / Vandenboorn, E.M.F. / Ottmann, C. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3 sigma /ER alpha Protein-Protein Interaction from Nonselective Fragments. Authors: Konstantinidou, M. / Visser, E.J. / Vandenboorn, E. / Chen, S. / Jaishankar, P. / Overmans, M. / Dutta, S. / Neitz, R.J. / Renslo, A.R. / Ottmann, C. / Brunsveld, L. / Arkin, M.R. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 122.4 KB | Display | ![]() |
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PDB format | ![]() | 92.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 763.2 KB | Display | ![]() |
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Full document | ![]() | 763.5 KB | Display | |
Data in XML | ![]() | 13.7 KB | Display | |
Data in CIF | ![]() | 20.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8ai0C ![]() 8alrC ![]() 8altC ![]() 8alvC ![]() 8alwC ![]() 8am7C ![]() 8anfC ![]() 8aoyC ![]() 8apsC ![]() 8aq1C ![]() 8aqcC ![]() 8aqeC ![]() 8aqzC ![]() 8ar4C ![]() 8ar5C ![]() 8argC ![]() 8aroC ![]() 8arqC ![]() 8arrC ![]() 8arwC ![]() 8arxC ![]() 8aryC ![]() 8arzC ![]() 8as1C ![]() 8atpC ![]() 8atrC ![]() 8atsC ![]() 8au2C ![]() 8ausC ![]() 8auyC ![]() 8av3C ![]() 8av4C ![]() 8av7C ![]() 8av8C ![]() 8awgC ![]() 8axeC ![]() 8axuC ![]() 8azeC ![]() 8b39C ![]() 4jc3S S: Starting model for refinement C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 26542.914 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein/peptide | Mass: 613.596 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
#3: Chemical | ChemComp-MG / |
#4: Chemical | ChemComp-NUO / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.64 Å3/Da / Density % sol: 53.46 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop Details: 0.095 M HEPES (pH 7.1), PEG400 (26% (v/v)), 0.19 M CaCl2 and 5% (v/v) Glycerol |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Aug 26, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.0332 Å / Relative weight: 1 |
Reflection | Resolution: 1.4→45.44 Å / Num. obs: 56855 / % possible obs: 99.9 % / Redundancy: 13 % / CC1/2: 0.998 / Net I/σ(I): 13.8 |
Reflection shell | Resolution: 1.4→1.42 Å / Num. unique obs: 2772 / CC1/2: 0.601 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 4JC3 Resolution: 1.4→45.44 Å / Cor.coef. Fo:Fc: 0.972 / Cor.coef. Fo:Fc free: 0.964 / SU B: 1.924 / SU ML: 0.034 / Cross valid method: THROUGHOUT / ESU R: 0.053 / ESU R Free: 0.051 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.5 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 20.682 Å2
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Refinement step | Cycle: LAST / Resolution: 1.4→45.44 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.4→1.436 Å / Total num. of bins used: 20
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