+Open data
-Basic information
Entry | Database: PDB / ID: 6chz | ||||||
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Title | Estrogen Receptor Alpha Y537S bound to antagonist H3B-9224. | ||||||
Components | Estrogen receptor | ||||||
Keywords | nuclear protein/antagonist / Nuclear hormone receptor / antagonist / activating mutation / breast cancer / NUCLEAR PROTEIN / nuclear protein-antagonist complex | ||||||
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 / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / nuclear estrogen receptor activity / epithelial cell proliferation involved in mammary gland duct elongation ...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 / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / nuclear estrogen receptor activity / epithelial cell proliferation involved in mammary gland duct elongation / prostate epithelial cord elongation / epithelial cell development / negative regulation of smooth muscle cell apoptotic process / mammary gland branching involved in pregnancy / uterus development / vagina development / androgen metabolic process / TFIIB-class transcription factor binding / steroid hormone mediated signaling pathway / mammary gland alveolus development / intracellular estrogen receptor signaling pathway / cellular response to estrogen stimulus / estrogen response element binding / positive regulation of phospholipase C activity / intracellular steroid hormone receptor signaling pathway / negative regulation of canonical NF-kappaB signal transduction / Nuclear signaling by ERBB4 / RNA polymerase II preinitiation complex assembly / protein localization to chromatin / TBP-class protein binding / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / steroid binding / nitric-oxide synthase regulator activity / ESR-mediated signaling / 14-3-3 protein binding / transcription corepressor binding / negative regulation of miRNA transcription / cellular response to estradiol stimulus / transcription coregulator binding / stem cell differentiation / nuclear estrogen receptor binding / positive regulation of nitric-oxide synthase activity / euchromatin / SUMOylation of intracellular receptors / negative regulation of DNA-binding transcription factor activity / transcription coactivator binding / beta-catenin binding / Nuclear Receptor transcription pathway / response to estrogen / male gonad development / Constitutive Signaling by Aberrant PI3K in Cancer / Regulation of RUNX2 expression and activity / nuclear receptor activity / positive regulation of nitric oxide biosynthetic process / positive regulation of DNA-binding transcription factor activity / positive regulation of fibroblast proliferation / Ovarian tumor domain proteases / sequence-specific double-stranded DNA binding / response to estradiol / PIP3 activates AKT signaling / phospholipase C-activating G protein-coupled receptor signaling pathway / ATPase binding / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / regulation of inflammatory response / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / DNA-binding transcription activator activity, RNA polymerase II-specific / Estrogen-dependent gene expression / transcription regulator complex / Extra-nuclear estrogen signaling / calmodulin binding / DNA-binding transcription factor activity, RNA polymerase II-specific / chromatin remodeling / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / negative regulation of gene expression / chromatin binding / chromatin / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / protein kinase binding / positive regulation of DNA-templated transcription / Golgi apparatus / negative regulation of transcription by RNA polymerase II / enzyme binding / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / zinc ion binding / nucleoplasm / membrane / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.68 Å | ||||||
Authors | Larsen, N.A. | ||||||
Citation | Journal: Cancer Discov / Year: 2018 Title: Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ER alphaWTand ER alphaMUTBreast Cancer. Authors: Puyang, X. / Furman, C. / Zheng, G.Z. / Wu, Z.J. / Banka, D. / Aithal, K. / Agoulnik, S. / Bolduc, D.M. / Buonamici, S. / Caleb, B. / Das, S. / Eckley, S. / Fekkes, P. / Hao, M.H. / Hart, A. ...Authors: Puyang, X. / Furman, C. / Zheng, G.Z. / Wu, Z.J. / Banka, D. / Aithal, K. / Agoulnik, S. / Bolduc, D.M. / Buonamici, S. / Caleb, B. / Das, S. / Eckley, S. / Fekkes, P. / Hao, M.H. / Hart, A. / Houtman, R. / Irwin, S. / Joshi, J.J. / Karr, C. / Kim, A. / Kumar, N. / Kumar, P. / Kuznetsov, G. / Lai, W.G. / Larsen, N. / Mackenzie, C. / Martin, L.A. / Melchers, D. / Moriarty, A. / Nguyen, T.V. / Norris, J. / O'Shea, M. / Pancholi, S. / Prajapati, S. / Rajagopalan, S. / Reynolds, D.J. / Rimkunas, V. / Rioux, N. / Ribas, R. / Siu, A. / Sivakumar, S. / Subramanian, V. / Thomas, M. / Vaillancourt, F.H. / Wang, J. / Wardell, S. / Wick, M.J. / Yao, S. / Yu, L. / Warmuth, M. / Smith, P.G. / Zhu, P. / Korpal, M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6chz.cif.gz | 70 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6chz.ent.gz | 50.3 KB | Display | PDB format |
PDBx/mmJSON format | 6chz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ch/6chz ftp://data.pdbj.org/pub/pdb/validation_reports/ch/6chz | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 30133.225 Da / Num. of mol.: 1 / Mutation: C381S, C417S, Y537S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ESR1, ESR, NR3A1 / Production host: Escherichia coli (E. coli) / References: UniProt: P03372 |
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#2: Chemical | ChemComp-F3D / |
#3: Chemical | ChemComp-EDO / |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.44 Å3/Da / Density % sol: 49.65 % |
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Crystal grow | Temperature: 296 K / Method: vapor diffusion, sitting drop Details: 6-12% PEG 3350, 50-150 mM MgCl2, 0.1 M imidazole pH 7.1 |
-Data collection
Diffraction | Mean temperature: 120 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 0.9787 Å |
Detector | Type: RAYONIX MX225-HS / Detector: CCD / Date: Nov 12, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9787 Å / Relative weight: 1 |
Reflection | Resolution: 1.68→50.76 Å / Num. obs: 33396 / % possible obs: 99.6 % / Redundancy: 9.4 % / Rmerge(I) obs: 0.109 / Net I/σ(I): 16.7 |
Reflection shell | Resolution: 1.68→1.74 Å / Rmerge(I) obs: 0.866 / Num. unique all: 1365 |
-Processing
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Refinement | Resolution: 1.68→50.76 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.925 / SU B: 3.009 / SU ML: 0.096 / Cross valid method: THROUGHOUT / ESU R: 0.111 / ESU R Free: 0.117 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 43.722 Å2
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Refinement step | Cycle: 1 / Resolution: 1.68→50.76 Å
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Refine LS restraints |
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