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Yorodumi- PDB-5fqs: Selective estrogen receptor downregulator antagonists: Tetrahydro... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5fqs | ||||||
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Title | Selective estrogen receptor downregulator antagonists: Tetrahydroisoquinoline phenols 3. | ||||||
Components | ESTROGEN RECEPTOR | ||||||
Keywords | SIGNALING PROTEIN / BREAST CANCER / ESTROGEN RECEPTOR DOWNREGULATOR / FULVESTRANT / THIQ / NUCLEAR HORMONE RECEPTOR | ||||||
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 / epithelial cell development / 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 / androgen metabolic process / steroid hormone receptor signaling pathway / 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 / estrogen response element binding / : / nuclear receptor-mediated steroid hormone signaling pathway / negative regulation of canonical NF-kappaB signal transduction / Nuclear signaling by ERBB4 / RNA polymerase II preinitiation complex assembly / negative regulation of miRNA transcription / protein localization to chromatin / 14-3-3 protein binding / cellular response to estradiol stimulus / transcription coregulator binding / nitric-oxide synthase regulator activity / steroid binding / TBP-class protein binding / ESR-mediated signaling / transcription corepressor binding / positive regulation of nitric-oxide synthase activity / SUMOylation of intracellular receptors / stem cell differentiation / nuclear estrogen receptor binding / 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 / nuclear receptor activity / transcription coactivator binding / beta-catenin binding / positive regulation of fibroblast proliferation / response to estrogen / Regulation of RUNX2 expression and activity / male gonad development / PIP3 activates AKT signaling / positive regulation of nitric oxide biosynthetic process / sequence-specific double-stranded DNA binding / Ovarian tumor domain proteases / regulation of inflammatory response / response to estradiol / ATPase binding / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / 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 / 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 / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / chromatin / regulation of DNA-templated transcription / protein kinase binding / enzyme binding / negative regulation of transcription by RNA polymerase II / Golgi apparatus / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / zinc ion binding / nucleoplasm / identical protein binding / membrane / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | HOMO SAPIENS (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / OTHER / Resolution: 1.94 Å | ||||||
Authors | Scott, J.S. / Bailey, A. / Davies, R.D.M. / Degorce, S.L. / MacFaul, P.A. / Gingell, H. / Moss, T. / Norman, R.A. / Pink, J.H. / Rabow, A.A. ...Scott, J.S. / Bailey, A. / Davies, R.D.M. / Degorce, S.L. / MacFaul, P.A. / Gingell, H. / Moss, T. / Norman, R.A. / Pink, J.H. / Rabow, A.A. / Roberts, B. / Smith, P.D. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2016 Title: Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat. Authors: Scott, J.S. / Bailey, A. / Davies, R.D.M. / Degorce, S.L. / MacFaul, P.A. / Gingell, H. / Moss, T. / Norman, R.A. / Pink, J.H. / Rabow, A.A. / Roberts, B. / Smith, P.D. #1: Journal: Cancer Res. / Year: 2016 Title: Azd9496: An Oral Estrogen Receptor Inhibitor that Blocks the Growth of Er-Positive and Esr1-Mutant Breast Tumors in Preclinical Models. Authors: Weir, H.M. / Bradbury, R.H. / Lawson, M. / Rabow, A.A. / Buttar, D. / Callis, R.J. / Curwen, J.O. / De Almeida, C. / Ballard, P. / Hulse, M. / Donald, C.S. / Feron, L.J.L. / Karoutchi, G. / ...Authors: Weir, H.M. / Bradbury, R.H. / Lawson, M. / Rabow, A.A. / Buttar, D. / Callis, R.J. / Curwen, J.O. / De Almeida, C. / Ballard, P. / Hulse, M. / Donald, C.S. / Feron, L.J.L. / Karoutchi, G. / Macfaul, P. / Moss, T. / Norman, R.A. / Pearson, S.E. / Tonge, M. / Davies, G. / Walker, G.E. / Wilson, Z. / Rowlinson, R. / Powell, S. / Sadler, C. / Richmond, G. / Ladd, B. / Pazolli, E. / Mazzola, A.M. / D'Cruz, C. / De Savi, C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5fqs.cif.gz | 106.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5fqs.ent.gz | 83.1 KB | Display | PDB format |
PDBx/mmJSON format | 5fqs.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fq/5fqs ftp://data.pdbj.org/pub/pdb/validation_reports/fq/5fqs | 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 on special symmetry positions |
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-Components
#1: Protein | Mass: 28258.113 Da / Num. of mol.: 1 / Fragment: LIGAND-BINDING DOMAIN, UNP RESIDUES 307-554 / Mutation: YES Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / Variant (production host): GOLD / References: UniProt: P03372 |
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#2: Chemical | ChemComp-J0W / ( |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
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-Sample preparation
Crystal | Density Matthews: 2.07 Å3/Da / Density % sol: 40.5 % / Description: NONE |
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Crystal grow | Details: 0.1 M PCTP, PH 6.5 (0.04 M SODIUM PROPIONATE, 0.02 M SODIUM CACODYLATE, 0.04 M BIS-TRIS PROPANE), 22% PEG3350, 0.2M MGCL2 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Type: DIAMOND / Wavelength: 1 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.95→50 Å / Num. obs: 20764 / % possible obs: 99.9 % / Observed criterion σ(I): 2 / Redundancy: 9 % / Rmerge(I) obs: 0.06 |
-Processing
Software | Name: REFMAC / Version: 5.7.0032 / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Refinement | Method to determine structure: OTHER Starting model: NONE Resolution: 1.94→50.56 Å / Cor.coef. Fo:Fc: 0.951 / Cor.coef. Fo:Fc free: 0.936 / SU B: 6.07 / SU ML: 0.089 / Cross valid method: THROUGHOUT / ESU R: 0.142 / ESU R Free: 0.136 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 26.921 Å2
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Refinement step | Cycle: LAST / Resolution: 1.94→50.56 Å
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Refine LS restraints |
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