[English] 日本語
Yorodumi
- PDB-5fqv: Selective estrogen receptor downregulator antagonists: Tetrahydro... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5fqv
TitleSelective estrogen receptor downregulator antagonists: Tetrahydroisoquinoline phenols 5.
ComponentsESTROGEN RECEPTOR ALPHA
KeywordsSIGNALING 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 / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / regulation of branching involved in prostate gland morphogenesis / prostate epithelial cord elongation / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / nuclear estrogen receptor activity ...regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / regulation of branching involved in prostate gland morphogenesis / prostate epithelial cord elongation / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / nuclear estrogen receptor activity / epithelial cell proliferation involved in mammary gland duct elongation / epithelial cell development / vagina development / mammary gland branching involved in pregnancy / negative regulation of smooth muscle cell apoptotic process / uterus development / TFIIB-class transcription factor binding / androgen metabolic process / steroid hormone receptor signaling pathway / mammary gland alveolus development / 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 / 14-3-3 protein binding / protein localization to chromatin / estrogen receptor signaling pathway / steroid binding / nitric-oxide synthase regulator activity / TBP-class protein binding / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / ESR-mediated signaling / transcription corepressor binding / negative regulation of miRNA transcription / positive regulation of nitric-oxide synthase activity / cellular response to estradiol stimulus / transcription coregulator binding / stem cell differentiation / nuclear estrogen receptor binding / positive regulation of DNA-binding transcription factor activity / SUMOylation of intracellular receptors / euchromatin / negative regulation of DNA-binding transcription factor activity / transcription coactivator binding / beta-catenin binding / Nuclear Receptor transcription pathway / response to estrogen / Constitutive Signaling by Aberrant PI3K in Cancer / male gonad development / nuclear receptor activity / Regulation of RUNX2 expression and activity / positive regulation of fibroblast proliferation / sequence-specific double-stranded DNA binding / positive regulation of nitric oxide biosynthetic process / Ovarian tumor domain proteases / PIP3 activates AKT signaling / response to estradiol / phospholipase C-activating G protein-coupled receptor signaling pathway / ATPase binding / regulation of inflammatory response / positive regulation of cytosolic calcium ion concentration / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / fibroblast proliferation / 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 / DNA-binding transcription factor activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of gene expression / chromatin binding / regulation of DNA-templated transcription / chromatin / 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 / identical protein binding / membrane / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Estrogen receptor / Oestrogen-type nuclear receptor final C-terminal domain / : / Oestrogen receptor / Oestrogen-type nuclear receptor final C-terminal / Estrogen receptor/oestrogen-related receptor / : / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormone receptor ...Estrogen receptor / Oestrogen-type nuclear receptor final C-terminal domain / : / Oestrogen receptor / Oestrogen-type nuclear receptor final C-terminal / Estrogen receptor/oestrogen-related receptor / : / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormone receptor / Nuclear hormones receptors DNA-binding region signature. / Zinc finger, nuclear hormone receptor-type / Zinc finger, C4 type (two domains) / Nuclear hormone receptors DNA-binding domain profile. / c4 zinc finger in nuclear hormone receptors / Nuclear hormone receptor, ligand-binding domain / Nuclear hormone receptor-like domain superfamily / Ligand-binding domain of nuclear hormone receptor / Nuclear receptor (NR) ligand-binding (LBD) domain profile. / Ligand binding domain of hormone receptors / Zinc finger, NHR/GATA-type / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-VQI / Estrogen receptor
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / OTHER / Resolution: 1.74 Å
AuthorsScott, 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
DepositionDec 14, 2015Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 10, 2016Provider: repository / Type: Initial release
Revision 1.1Oct 12, 2016Group: Database references
Revision 1.2May 8, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: ESTROGEN RECEPTOR ALPHA
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,6242
Polymers28,2581
Non-polymers3651
Water1,892105
1
A: ESTROGEN RECEPTOR ALPHA
hetero molecules

A: ESTROGEN RECEPTOR ALPHA
hetero molecules


Theoretical massNumber of molelcules
Total (without water)57,2474
Polymers56,5162
Non-polymers7312
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation11_555-x+y,y,-z+1/21
Buried area2970 Å2
ΔGint-13.8 kcal/mol
Surface area20130 Å2
MethodPISA
Unit cell
Length a, b, c (Å)58.329, 58.329, 275.591
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number179
Space group name H-MP6522
Components on special symmetry positions
IDModelComponents
11A-2025-

HOH

21A-2098-

HOH

-
Components

#1: Protein ESTROGEN RECEPTOR ALPHA / ER / ER-ALPHA / ESTRADIOL RECEPTOR / NUCLEAR RECEPTOR SUBFAMILY 3 GROUP A MEMBER 1 / ESTROGEN RECEPTOR ALPHA


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
#2: Chemical ChemComp-VQI / (E)-3-[4-(6-hydroxy-2-isobutyl-7-methyl-3,4-dihydro-1H-isoquinolin-1-yl)phenyl]prop-2-enoic acid


Mass: 365.465 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H27NO3
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 105 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 2.07 Å3/Da / Density % sol: 40.5 % / Description: NONE
Crystal growDetails: 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

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Type: DIAMOND / Wavelength: 1
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.75→50 Å / Num. obs: 28117 / % possible obs: 100 % / Observed criterion σ(I): 2 / Redundancy: 12 % / Rmerge(I) obs: 0.07

-
Processing

SoftwareName: REFMAC / Version: 5.7.0032 / Classification: refinement
RefinementMethod to determine structure: OTHER
Starting model: NONE

Resolution: 1.74→50.51 Å / Cor.coef. Fo:Fc: 0.955 / Cor.coef. Fo:Fc free: 0.944 / SU B: 4.437 / SU ML: 0.073 / Cross valid method: THROUGHOUT / ESU R: 0.107 / ESU R Free: 0.11 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.2336 1503 5.1 %RANDOM
Rwork0.1931 ---
obs0.19514 28117 99.99 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Refinement stepCycle: LAST / Resolution: 1.74→50.51 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1842 0 27 105 1974
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.020.0191917
X-RAY DIFFRACTIONr_bond_other_d0.0010.021850
X-RAY DIFFRACTIONr_angle_refined_deg1.911.9932599
X-RAY DIFFRACTIONr_angle_other_deg0.94534246
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.9055232
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.76824.37580
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.46715345
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.952159
X-RAY DIFFRACTIONr_chiral_restr0.2930.2304
X-RAY DIFFRACTIONr_gen_planes_refined0.010.022105
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02415
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it2.0182.091934
X-RAY DIFFRACTIONr_mcbond_other2.0092.09933
X-RAY DIFFRACTIONr_mcangle_it2.7573.1231164
X-RAY DIFFRACTIONr_mcangle_other2.7593.1231165
X-RAY DIFFRACTIONr_scbond_it3.3582.448982
X-RAY DIFFRACTIONr_scbond_other3.3732.465951
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other4.9733.5571394
X-RAY DIFFRACTIONr_long_range_B_refined6.17717.4572219
X-RAY DIFFRACTIONr_long_range_B_other6.12217.1922134
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.744→1.789 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.323 101 -
Rwork0.23 2010 -
obs--100 %
Refinement TLS params.Method: refined / Origin x: 12.7089 Å / Origin y: 33.9311 Å / Origin z: 69.295 Å
111213212223313233
T0.0092 Å2-0.0182 Å20.0008 Å2-0.0365 Å2-0 Å2--0.0206 Å2
L0.4363 °2-0.4256 °2-0.1637 °2-0.4164 °20.1751 °2--0.6149 °2
S0.0011 Å °-0.0055 Å °0.0199 Å °-0.0049 Å °0.0063 Å °-0.0152 Å °-0.0533 Å °0.1169 Å °-0.0074 Å °

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more