[English] 日本語
Yorodumi
- PDB-4pxm: The Estrogen Receptor Alpha Ligand Binding Domain D538G Mutant in... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4pxm
TitleThe Estrogen Receptor Alpha Ligand Binding Domain D538G Mutant in Complex with Estradiol and a glucocorticoid receptor-interacting protein 1 NR box II peptide
Components
  • Estrogen receptor
  • Nuclear receptor coactivator 2
KeywordsHormone/Peptide / Metastatic Breast Cancer / Activating Mutation / ER alpha / Alpha Helical / Nuclear Hormone Receptor / Hormone-Peptide complex
Function / homology
Function and homology information


RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / steroid hormone receptor signaling pathway / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / nuclear estrogen receptor activity / locomotor rhythm / Developmental Lineage of Mammary Gland Alveolar Cells / aryl hydrocarbon receptor binding / TFIIB-class transcription factor binding / regulation of glucose metabolic process ...RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / steroid hormone receptor signaling pathway / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / nuclear estrogen receptor activity / locomotor rhythm / Developmental Lineage of Mammary Gland Alveolar Cells / aryl hydrocarbon receptor binding / TFIIB-class transcription factor binding / regulation of glucose metabolic process / negative regulation of smooth muscle cell apoptotic process / Synthesis of bile acids and bile salts / nuclear receptor-mediated steroid hormone signaling pathway / cellular response to estrogen stimulus / Developmental Lineage of Mammary Gland Luminal Epithelial Cells / estrogen response element binding / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / regulation of lipid metabolic process / Endogenous sterols / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / Mitochondrial unfolded protein response (UPRmt) / Nuclear signaling by ERBB4 / Recycling of bile acids and salts / estrogen receptor signaling pathway / transcription regulator inhibitor activity / RNA polymerase II preinitiation complex assembly / cellular response to hormone stimulus / positive regulation of nitric-oxide synthase activity / steroid binding / peroxisome proliferator activated receptor signaling pathway / Regulation of lipid metabolism by PPARalpha / stem cell differentiation / positive regulation of adipose tissue development / protein localization to chromatin / bile acid and bile salt transport / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / BMAL1:CLOCK,NPAS2 activates circadian expression / regulation of cellular response to insulin stimulus / 14-3-3 protein binding / RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression / SUMOylation of transcription cofactors / Expression of BMAL (ARNTL), CLOCK, and NPAS2 / Activation of gene expression by SREBF (SREBP) / ESR-mediated signaling / negative regulation of miRNA transcription / negative regulation of smoothened signaling pathway / TBP-class protein binding / nitric-oxide synthase regulator activity / nuclear receptor binding / nuclear estrogen receptor binding / transcription corepressor binding / transcription coregulator binding / negative regulation of canonical NF-kappaB signal transduction / cellular response to estradiol stimulus / SUMOylation of intracellular receptors / circadian regulation of gene expression / Heme signaling / PPARA activates gene expression / Cytoprotection by HMOX1 / Transcriptional activation of mitochondrial biogenesis / Transcriptional regulation of white adipocyte differentiation / euchromatin / Nuclear Receptor transcription pathway / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / mRNA transcription by RNA polymerase II / response to estrogen / beta-catenin binding / nuclear receptor activity / positive regulation of nitric oxide biosynthetic process / transcription coregulator activity / Constitutive Signaling by Aberrant PI3K in Cancer / sequence-specific double-stranded DNA binding / transcription coactivator binding / phospholipase C-activating G protein-coupled receptor signaling pathway / Regulation of RUNX2 expression and activity / response to estradiol / Ovarian tumor domain proteases / PIP3 activates AKT signaling / HATs acetylate histones / ATPase binding / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / positive regulation of cytosolic calcium ion concentration / DNA-binding transcription activator activity, RNA polymerase II-specific / Estrogen-dependent gene expression / calmodulin binding / nuclear body / DNA-binding transcription factor activity, RNA polymerase II-specific / transcription coactivator activity / Extra-nuclear estrogen signaling / protein dimerization activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / chromatin remodeling / DNA-binding transcription factor activity / negative regulation of gene expression / protein domain specific binding / chromatin binding / regulation of transcription by RNA polymerase II / regulation of DNA-templated transcription / positive regulation of DNA-templated transcription
Similarity search - Function
Nuclear receptor coactivator 2 / Nuclear receptor coactivator 2/3, DUF4927 / Domain of unknown function (DUF4927) / Oestrogen-type nuclear receptor final C-terminal domain / Oestrogen-type nuclear receptor final C-terminal / Estrogen receptor / : / Oestrogen receptor / Estrogen receptor/oestrogen-related receptor / Nuclear receptor coactivator, DUF1518 ...Nuclear receptor coactivator 2 / Nuclear receptor coactivator 2/3, DUF4927 / Domain of unknown function (DUF4927) / Oestrogen-type nuclear receptor final C-terminal domain / Oestrogen-type nuclear receptor final C-terminal / Estrogen receptor / : / Oestrogen receptor / 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 / Nuclear receptor coactivators bHLH domain / PAS domain / : / Nuclear receptor coactivator, interlocking / helix loop helix domain / Myc-type, basic helix-loop-helix (bHLH) domain / Myc-type, basic helix-loop-helix (bHLH) domain profile. / Helix-loop-helix DNA-binding domain superfamily / PAS fold / PAS fold / PAS domain / PAS repeat profile. / PAS domain / Retinoid X Receptor / Retinoid X Receptor / PAS domain superfamily / Nuclear hormone receptor / Nuclear hormones receptors DNA-binding region signature. / Zinc finger, nuclear hormone receptor-type / Double treble clef zinc finger, C4 type / 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
ESTRADIOL / Estrogen receptor / Nuclear receptor coactivator 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsFanning, S.W. / Panchamukhi, S. / Greene, G.L.
CitationJournal: Elife / Year: 2016
Title: Estrogen receptor alpha somatic mutations Y537S and D538G confer breast cancer endocrine resistance by stabilizing the activating function-2 binding conformation.
Authors: Fanning, S.W. / Mayne, C.G. / Dharmarajan, V. / Carlson, K.E. / Martin, T.A. / Novick, S.J. / Toy, W. / Green, B. / Panchamukhi, S. / Katzenellenbogen, B.S. / Tajkhorshid, E. / Griffin, P.R. ...Authors: Fanning, S.W. / Mayne, C.G. / Dharmarajan, V. / Carlson, K.E. / Martin, T.A. / Novick, S.J. / Toy, W. / Green, B. / Panchamukhi, S. / Katzenellenbogen, B.S. / Tajkhorshid, E. / Griffin, P.R. / Shen, Y. / Chandarlapaty, S. / Katzenellenbogen, J.A. / Greene, G.L.
History
DepositionMar 24, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 8, 2015Provider: repository / Type: Initial release
Revision 1.1Feb 24, 2016Group: Database references
Revision 1.2May 17, 2017Group: Structure summary
Revision 1.3Feb 28, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _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
B: Estrogen receptor
C: Nuclear receptor coactivator 2
D: Nuclear receptor coactivator 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)65,4816
Polymers64,9364
Non-polymers5452
Water1,56787
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6240 Å2
ΔGint-33 kcal/mol
Surface area19440 Å2
MethodPISA
Unit cell
Length a, b, c (Å)56.084, 84.182, 58.372
Angle α, β, γ (deg.)90.00, 108.83, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Estrogen receptor / ER / ER-alpha / Estradiol receptor / Nuclear receptor subfamily 3 group A member 1


Mass: 30888.252 Da / Num. of mol.: 2 / Fragment: D538G
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ESR, ESR1, NR3A1 / Production host: Escherichia coli (E. coli) / References: UniProt: P03372
#2: Protein/peptide Nuclear receptor coactivator 2 / NCoA-2 / Class E basic helix-loop-helix protein 75 / bHLHe75 / Transcriptional intermediary factor 2 / hTIF2


Mass: 1579.866 Da / Num. of mol.: 2 / Source method: obtained synthetically / Details: Peptide Synthesis / Source: (synth.) Homo sapiens (human) / References: UniProt: Q15596
#3: Chemical ChemComp-EST / ESTRADIOL


Mass: 272.382 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C18H24O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 87 / 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: 2.01 Å3/Da / Density % sol: 38.76 %
Crystal growTemperature: 298.15 K / Method: vapor diffusion, hanging drop / pH: 8
Details: 20% PEG 3,350, 1 mM Phenylalanine, 64 mM NaCl, 50 mM MgCl2, pH 8.0, VAPOR DIFFUSION, HANGING DROP, temperature 298.15K

-
Data collection

Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 0.97 Å
DetectorType: MAR scanner 300 mm plate / Detector: IMAGE PLATE / Date: Feb 20, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97 Å / Relative weight: 1
ReflectionResolution: 1.89→55.25 Å / Num. obs: 9605 / % possible obs: 99.8 % / Observed criterion σ(F): 5 / Observed criterion σ(I): 2

-
Processing

Software
NameVersionClassification
HKL-3000data collection
PHASERphasing
REFMAC5.6.0117refinement
HKL-3000data reduction
HKL-3000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.9→55.25 Å / Cor.coef. Fo:Fc: 0.962 / Cor.coef. Fo:Fc free: 0.95 / SU B: 6.743 / SU ML: 0.092 / Cross valid method: THROUGHOUT / σ(F): 5 / ESU R: 0.145 / ESU R Free: 0.133 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
RfactorNum. reflection% reflectionSelection details
Rfree0.21417 2018 5 %RANDOM
Rwork0.17935 ---
obs0.18112 -99.27 %-
all-40344 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 34.335 Å2
Baniso -1Baniso -2Baniso -3
1--0.47 Å2-0 Å20.4 Å2
2--2.01 Å2-0 Å2
3----1.28 Å2
Refinement stepCycle: LAST / Resolution: 1.9→55.25 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3744 0 40 87 3871
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0170.0193929
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.5441.9885314
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.8775473
X-RAY DIFFRACTIONr_dihedral_angle_2_deg38.66123.72164
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.28315742
X-RAY DIFFRACTIONr_dihedral_angle_4_deg24.0941523
X-RAY DIFFRACTIONr_chiral_restr0.1270.2631
X-RAY DIFFRACTIONr_gen_planes_refined0.0120.0212808
X-RAY DIFFRACTIONr_gen_planes_other
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_it
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.898→1.947 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.279 143 -
Rwork0.236 2650 -
obs--94.77 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.6095-0.1738-0.86340.34840.17090.7450.05690.1430.0378-0.0369-0.0183-0.0241-0.0367-0.0513-0.03850.02970.00970.00120.04680.00740.005815.11450.87515.3815
21.263-0.06660.50820.5669-0.17551.5643-0.0335-0.0424-0.02650.11950.00890.0259-0.08660.01660.02460.03990.00240.00820.0054-0.00110.00875.93472.365229.2434
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A307 - 549
2X-RAY DIFFRACTION1A2000
3X-RAY DIFFRACTION1A2101 - 2138
4X-RAY DIFFRACTION2B305 - 548
5X-RAY DIFFRACTION2B2000
6X-RAY DIFFRACTION2B2101 - 2149

+
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