+Open data
-Basic information
Entry | Database: PDB / ID: 8aq1 | ||||||
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Title | small molecule stabilizer for ERalpha and 14-3-3 (1083743) | ||||||
Components |
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Keywords | STRUCTURAL PROTEIN / 14-3-3 / ERalpha / stabilization / 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 / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / estrogen receptor signaling pathway / cellular response to estrogen stimulus / establishment of skin barrier / 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 / negative regulation of miRNA transcription / protein localization to chromatin / 14-3-3 protein binding / cellular response to estradiol stimulus / protein sequestering activity / protein kinase A signaling / transcription coregulator binding / negative regulation of innate immune response / nitric-oxide synthase regulator activity / steroid binding / TBP-class protein binding / protein export from nucleus / ESR-mediated signaling / transcription corepressor binding / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / release of cytochrome c from mitochondria / positive regulation of protein export from nucleus / positive regulation of nitric-oxide synthase activity / stem cell proliferation / SUMOylation of intracellular receptors / 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 / positive regulation of DNA-binding transcription factor activity / Nuclear Receptor transcription pathway / euchromatin / negative regulation of DNA-binding transcription factor activity / Constitutive Signaling by Aberrant PI3K in Cancer / transcription coactivator binding / nuclear receptor activity / beta-catenin binding / positive regulation of fibroblast proliferation / response to estrogen / Regulation of RUNX2 expression and activity / male gonad development / intrinsic apoptotic signaling pathway in response to DNA damage / PIP3 activates AKT signaling / positive regulation of nitric oxide biosynthetic process / sequence-specific double-stranded DNA binding / protein localization / Ovarian tumor domain proteases / regulation of inflammatory response / response to estradiol / ATPase binding / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / positive regulation of cell growth / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / DNA-binding transcription activator activity, RNA polymerase II-specific / fibroblast proliferation / transcription regulator complex / Estrogen-dependent gene expression / Extra-nuclear estrogen signaling Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.4 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 | 8aq1.cif.gz | 73.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8aq1.ent.gz | 51.1 KB | Display | PDB format |
PDBx/mmJSON format | 8aq1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8aq1_validation.pdf.gz | 749.1 KB | Display | wwPDB validaton report |
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Full document | 8aq1_full_validation.pdf.gz | 749.7 KB | Display | |
Data in XML | 8aq1_validation.xml.gz | 15 KB | Display | |
Data in CIF | 8aq1_validation.cif.gz | 23.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/aq/8aq1 ftp://data.pdbj.org/pub/pdb/validation_reports/aq/8aq1 | HTTPS FTP |
-Related structure data
Related structure data | 8ai0C 8alrC 8altC 8alvC 8alwC 8am7C 8anfC 8aoyC 8apsC 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-NJC / ( | #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, hanging 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: 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: 1.4→41.84 Å / Num. obs: 57400 / % possible obs: 100 % / Redundancy: 12.8 % / CC1/2: 0.991 / Net I/σ(I): 25.1 |
Reflection shell | Resolution: 1.4→1.42 Å / Num. unique obs: 2810 / CC1/2: 0.967 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4JC3 Resolution: 1.4→41.16 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.951 / SU B: 0.751 / SU ML: 0.03 / Cross valid method: THROUGHOUT / ESU R: 0.052 / ESU R Free: 0.053 / 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: 1.1 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 12.251 Å2
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Refinement step | Cycle: LAST / Resolution: 1.4→41.16 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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