[English] 日本語
Yorodumi
- PDB-3omq: Fragment-Based Design of novel Estrogen Receptor Ligands -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3omq
TitleFragment-Based Design of novel Estrogen Receptor Ligands
Components
  • Estrogen receptor beta
  • Nuclear receptor coactivator 1
KeywordsPROTEIN BINDING / Steroid binding
Function / homology
Function and homology information


receptor antagonist activity / labyrinthine layer morphogenesis / regulation of thyroid hormone mediated signaling pathway / positive regulation of transcription from RNA polymerase II promoter by galactose / positive regulation of female receptivity / nuclear steroid receptor activity / hypothalamus development / male mating behavior / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / nuclear estrogen receptor activity ...receptor antagonist activity / labyrinthine layer morphogenesis / regulation of thyroid hormone mediated signaling pathway / positive regulation of transcription from RNA polymerase II promoter by galactose / positive regulation of female receptivity / nuclear steroid receptor activity / hypothalamus development / male mating behavior / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / nuclear estrogen receptor activity / estrous cycle / cellular response to Thyroglobulin triiodothyronine / Synthesis of bile acids and bile salts / intracellular estrogen receptor signaling pathway / cellular response to estrogen stimulus / Endogenous sterols / estrogen response element binding / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / nuclear retinoid X receptor binding / response to retinoic acid / histone acetyltransferase activity / regulation of cellular response to insulin stimulus / Recycling of bile acids and salts / histone acetyltransferase / cellular response to hormone stimulus / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / positive regulation of adipose tissue development / peroxisome proliferator activated receptor signaling pathway / RORA activates gene expression / lactation / positive regulation of neuron differentiation / Regulation of lipid metabolism by PPARalpha / steroid binding / cerebellum development / ESR-mediated signaling / BMAL1:CLOCK,NPAS2 activates circadian gene expression / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / nuclear receptor coactivator activity / response to progesterone / cellular response to estradiol stimulus / nuclear estrogen receptor binding / nuclear receptor binding / hippocampus development / RNA polymerase II transcription regulatory region sequence-specific DNA binding / Heme signaling / mRNA transcription by RNA polymerase II / Transcriptional activation of mitochondrial biogenesis / negative regulation of cell growth / PPARA activates gene expression / Cytoprotection by HMOX1 / cerebral cortex development / positive regulation of DNA-binding transcription factor activity / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / RNA polymerase II transcription regulator complex / Constitutive Signaling by Aberrant PI3K in Cancer / nuclear receptor activity / male gonad development / Circadian Clock / PIP3 activates AKT signaling / response to estradiol / cell-cell signaling / HATs acetylate histones / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / Estrogen-dependent gene expression / transcription regulator complex / Extra-nuclear estrogen signaling / transcription coactivator activity / protein dimerization activity / DNA-binding transcription factor activity, RNA polymerase II-specific / positive regulation of apoptotic process / RNA polymerase II cis-regulatory region sequence-specific DNA binding / intracellular membrane-bounded organelle / chromatin binding / chromatin / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / enzyme binding / negative regulation of transcription by RNA polymerase II / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / mitochondrion / DNA binding / zinc ion binding / nucleoplasm / nucleus / plasma membrane / cytosol
Similarity search - Function
Estrogen receptor beta-like, N-terminal / Estrogen receptor beta/gamma / Estrogen receptor beta / Nuclear receptor coactivator 1 / Estrogen receptor/oestrogen-related receptor / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator, Ncoa-type, interlocking / Nuclear receptor coactivator, Ncoa-type, interlocking domain superfamily / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator ...Estrogen receptor beta-like, N-terminal / Estrogen receptor beta/gamma / Estrogen receptor beta / Nuclear receptor coactivator 1 / Estrogen receptor/oestrogen-related receptor / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator, Ncoa-type, interlocking / Nuclear receptor coactivator, Ncoa-type, interlocking domain superfamily / Nuclear receptor coactivator, DUF1518 / Nuclear receptor coactivator / DUF1518 / Nuclear receptor coactivator, receptor-binding domain / Nuclear receptor coactivator / Steroid receptor coactivator / Unstructured region on nuclear receptor coactivator protein / PAS domain / Nuclear receptor coactivator, interlocking / Helix-loop-helix DNA-binding domain superfamily / helix loop helix domain / Myc-type, basic helix-loop-helix (bHLH) domain / Myc-type, basic helix-loop-helix (bHLH) domain profile. / PAS fold / PAS fold / PAS domain / PAS repeat profile. / PAS domain / PAS domain superfamily / 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-W23 / Nuclear receptor coactivator 1 / Estrogen receptor beta
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.97 Å
AuthorsMoecklinghoff, S. / van Otterlo, W.A. / Rose, R. / Fuchs, S. / Dominguez Seoane, M. / Waldmann, H. / Ottmann, C. / Brunsveld, L.
CitationJournal: J.Med.Chem. / Year: 2011
Title: Design and Evaluation of Fragment-Like Estrogen Receptor Tetrahydroisoquinoline Ligands from a Scaffold-Detection Approach.
Authors: van Otterlo, W.A. / Rose, R. / Fuchs, S. / Zimmermann, T.J. / Dominguez Seoane, M. / Waldmann, H. / Ottmann, C. / Brunsveld, L.
History
DepositionAug 27, 2010Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 16, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Feb 21, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _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 beta
B: Estrogen receptor beta
C: Nuclear receptor coactivator 1
D: Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)59,2506
Polymers58,6874
Non-polymers5632
Water5,999333
1
A: Estrogen receptor beta
C: Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,6253
Polymers29,3442
Non-polymers2811
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1100 Å2
ΔGint-8 kcal/mol
Surface area11590 Å2
MethodPISA
2
B: Estrogen receptor beta
D: Nuclear receptor coactivator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,6253
Polymers29,3442
Non-polymers2811
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1010 Å2
ΔGint-8 kcal/mol
Surface area11630 Å2
MethodPISA
3


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4930 Å2
ΔGint-33 kcal/mol
Surface area20400 Å2
MethodPISA
Unit cell
Length a, b, c (Å)70.590, 70.590, 110.090
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number144
Space group name H-MP31
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B

NCS domain segments:
Dom-IDComponent-IDEns-IDRefine codeAuth asym-IDAuth seq-ID
1114A1 - 1000
2114B1 - 1000

-
Components

#1: Protein Estrogen receptor beta / / ER-beta / Nuclear receptor subfamily 3 group A member 2


Mass: 27109.143 Da / Num. of mol.: 2 / Fragment: Ligand Binding Domain (UNP residues 261-500)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ESR2, ESTRB, NR3A2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q92731
#2: Protein/peptide Nuclear receptor coactivator 1 / / NCoA-1 / Steroid receptor coactivator 1 / SRC-1 / RIP160 / Protein Hin-2 / Renal carcinoma antigen ...NCoA-1 / Steroid receptor coactivator 1 / SRC-1 / RIP160 / Protein Hin-2 / Renal carcinoma antigen NY-REN-52 / Class E basic helix-loop-helix protein 74 / bHLHe74


Mass: 2234.535 Da / Num. of mol.: 2 / Fragment: Box 2 (UNP residues 683-701) / Source method: obtained synthetically / Details: Synthetic peptide / References: UniProt: Q15788
#3: Chemical ChemComp-W23 / 2-[(trifluoromethyl)sulfonyl]-1,2,3,4-tetrahydroisoquinolin-6-ol


Mass: 281.252 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H10F3NO3S
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 333 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.7 Å3/Da / Density % sol: 54.42 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, hanging drop / pH: 5.5
Details: 0.2 M Ammonium Acetate, 0.1 M BIS-TRIS pH 5.5, 17% PEG10000 (v/v), VAPOR DIFFUSION, HANGING DROP, temperature 277.15K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU / Wavelength: 1.5418 Å
DetectorType: MARRESEARCH / Detector: AREA DETECTOR / Date: Jul 11, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.95→20 Å / Num. obs: 42278 / % possible obs: 94.5 % / Observed criterion σ(I): -3 / Biso Wilson estimate: 27.425 Å2 / Rmerge(I) obs: 0.051 / Net I/σ(I): 13.03
Reflection shell
Resolution (Å)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. unique obs% possible all
1.95-2.20.2074.1237831175686.4
2.2-2.50.1177.320473979198.9
2.5-30.06911.718796884998.9
3-3.50.039209584447398
3.5-40.02628.75217241695.4
4-50.02133.85302244596.2
5-100.0232.35049228097.9
10-150.01248.950721995.2
15-200.01544.71114989.1

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
XSCALEdata scaling
PHASERphasing
REFMAC5.5.0109refinement
PDB_EXTRACT3.1data extraction
XDSdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.97→19.55 Å / Cor.coef. Fo:Fc: 0.932 / Cor.coef. Fo:Fc free: 0.902 / Occupancy max: 1 / Occupancy min: 0.5 / SU B: 9.441 / SU ML: 0.12 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.167 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. U VALUES: REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.26 2113 5 %RANDOM
Rwork0.2051 ---
obs0.2079 42274 100 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso max: 122.89 Å2 / Biso mean: 22.0894 Å2 / Biso min: 6.07 Å2
Baniso -1Baniso -2Baniso -3
1-0.32 Å20.16 Å20 Å2
2--0.32 Å20 Å2
3----0.48 Å2
Refinement stepCycle: LAST / Resolution: 1.97→19.55 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3747 0 36 333 4116
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0230.0223871
X-RAY DIFFRACTIONr_angle_refined_deg1.9482.0025240
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.5455471
X-RAY DIFFRACTIONr_dihedral_angle_2_deg42.28123.889144
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.56615746
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.3141521
X-RAY DIFFRACTIONr_chiral_restr0.1360.2626
X-RAY DIFFRACTIONr_gen_planes_refined0.010.0212727
X-RAY DIFFRACTIONr_mcbond_it1.6261.52377
X-RAY DIFFRACTIONr_mcangle_it2.60423843
X-RAY DIFFRACTIONr_scbond_it4.60631494
X-RAY DIFFRACTIONr_scangle_it6.5184.51397
X-RAY DIFFRACTIONr_rigid_bond_restr2.57133871
Refine LS restraints NCS

Dom-ID: 1 / Auth asym-ID: A / Ens-ID: 1 / Number: 1745 / Refine-ID: X-RAY DIFFRACTION

TypeRms dev position (Å)Weight position
MEDIUM POSITIONAL0.320.5
MEDIUM THERMAL0.962
LS refinement shellResolution: 1.971→2.021 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.341 140 -
Rwork0.304 2670 -
all-2810 -
obs--100 %

+
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