+Open data
-Basic information
Entry | Database: PDB / ID: 8aps | ||||||
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Title | Small molecular stabilizer for ERalpha and 14-3-3 (1083744) | ||||||
Components |
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Keywords | STRUCTURAL PROTEIN / 14-3-3 / ERalpha / stabilization / 1080272 / covalent | ||||||
Function / homology | Function and homology information 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 / steroid binding / protein export from nucleus / 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 / regulation of inflammatory response / fibroblast proliferation / 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 | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.2 Å | ||||||
Authors | Visser, E.J. / Vandenboorn, E.M.F. / Ottmann, C. | ||||||
Funding support | Netherlands, 1items
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Citation | Journal: J.Am.Chem.Soc. / Year: 2023 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8aps.cif.gz | 127.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8aps.ent.gz | 96.1 KB | Display | PDB format |
PDBx/mmJSON format | 8aps.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8aps_validation.pdf.gz | 784.3 KB | Display | wwPDB validaton report |
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Full document | 8aps_full_validation.pdf.gz | 785.2 KB | Display | |
Data in XML | 8aps_validation.xml.gz | 14.4 KB | Display | |
Data in CIF | 8aps_validation.cif.gz | 22.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ap/8aps ftp://data.pdbj.org/pub/pdb/validation_reports/ap/8aps | HTTPS FTP |
-Related structure data
Related structure data | 8ai0C 8alrC 8altC 8alvC 8alwC 8am7C 8anfC 8aoyC 8aq1C 8aqcC 8aqeC 8aqzC 8ar4C 8ar5C 8argC 8aroC 8arqC 8arrC 8arwC 8arxC 8aryC 8arzC 8as1C 8at9C 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 (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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Components on special symmetry positions |
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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.) Homo sapiens (human) / Gene: SFN, HME1 / Production host: Escherichia coli (E. coli) / References: UniProt: P31947 | ||||||
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#2: Protein/peptide | Mass: 613.596 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P03372 | ||||||
#3: Chemical | #4: Chemical | ChemComp-NJ3 / | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.68 Å3/Da / Density % sol: 54.17 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop Details: 0.095 M HEPES (pH 7.3), PEG400 (24% (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: SYNCHROTRON / Site: ESRF / Beamline: ID23-2 / Wavelength: 0.873128 Å |
Detector | Type: DECTRIS PILATUS3 2M / Detector: PIXEL / Date: Jan 29, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.873128 Å / Relative weight: 1 |
Reflection | Resolution: 1.2→41.95 Å / Num. obs: 90357 / % possible obs: 99 % / Redundancy: 11.6 % / CC1/2: 0.653 / Net I/σ(I): 22.2 |
Reflection shell | Resolution: 1.2→1.22 Å / Num. unique obs: 4159 / CC1/2: 0.945 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4JC3 Resolution: 1.2→41.94 Å / Cor.coef. Fo:Fc: 0.972 / Cor.coef. Fo:Fc free: 0.966 / SU B: 0.809 / SU ML: 0.017 / Cross valid method: THROUGHOUT / ESU R: 0.031 / ESU R Free: 0.03 / 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: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 84.72 Å2 / Biso mean: 12.483 Å2 / Biso min: 2.52 Å2
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Refinement step | Cycle: final / Resolution: 1.2→41.94 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.2→1.231 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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