[English] 日本語
Yorodumi
- PDB-4p6x: Crystal Structure of cortisol-bound glucocorticoid receptor ligan... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4p6x
TitleCrystal Structure of cortisol-bound glucocorticoid receptor ligand binding domain
Components
  • Glucocorticoid receptor
  • Nuclear receptor coactivator 2
KeywordsHORMONE RECEPTOR/HORMONE ACTIVATOR / cortisol / glucocorticoid receptor / potency / HORMONE-HORMONE RECEPTOR complex / HORMONE RECEPTOR-HORMONE ACTIVATOR complex
Function / homology
Function and homology information


Regulation of NPAS4 gene transcription / regulation of glucocorticoid biosynthetic process / nuclear glucocorticoid receptor activity / steroid hormone binding / PTK6 Expression / glucocorticoid metabolic process / neuroinflammatory response / microglia differentiation / maternal behavior / mammary gland duct morphogenesis ...Regulation of NPAS4 gene transcription / regulation of glucocorticoid biosynthetic process / nuclear glucocorticoid receptor activity / steroid hormone binding / PTK6 Expression / glucocorticoid metabolic process / neuroinflammatory response / microglia differentiation / maternal behavior / mammary gland duct morphogenesis / nucleus localization / astrocyte differentiation / cellular response to glucocorticoid stimulus / motor behavior / regulation of gluconeogenesis / adrenal gland development / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / cellular response to steroid hormone stimulus / locomotor rhythm / aryl hydrocarbon receptor binding / regulation of lipid metabolic process / cellular response to Thyroglobulin triiodothyronine / regulation of glucose metabolic process / Synthesis of bile acids and bile salts / Endogenous sterols / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / estrogen response element binding / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / intracellular steroid hormone receptor signaling pathway / core promoter sequence-specific DNA binding / Recycling of bile acids and salts / regulation of cellular response to insulin stimulus / cellular response to hormone stimulus / cellular response to transforming growth factor beta stimulus / positive regulation of adipose tissue development / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / peroxisome proliferator activated receptor signaling pathway / RORA activates gene expression / TBP-class protein binding / Regulation of lipid metabolism by PPARalpha / steroid binding / cellular response to dexamethasone stimulus / BMAL1:CLOCK,NPAS2 activates circadian gene expression / nuclear receptor coactivator activity / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / response to progesterone / synaptic transmission, glutamatergic / chromosome segregation / nuclear receptor binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / Hsp90 protein binding / circadian regulation of gene expression / Heme signaling / SUMOylation of intracellular receptors / mRNA transcription by RNA polymerase II / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / Cytoprotection by HMOX1 / spindle / DNA-binding transcription repressor activity, RNA polymerase II-specific / Transcriptional regulation of white adipocyte differentiation / positive regulation of miRNA transcription / Nuclear Receptor transcription pathway / RNA polymerase II transcription regulator complex / positive regulation of neuron apoptotic process / Regulation of RUNX2 expression and activity / nuclear receptor activity / Circadian Clock / sequence-specific double-stranded DNA binding / gene expression / chromatin organization / HATs acetylate histones / DNA-binding transcription activator activity, RNA polymerase II-specific / Estrogen-dependent gene expression / transcription regulator complex / Potential therapeutics for SARS / transcription coactivator activity / protein dimerization activity / nuclear body / DNA-binding transcription factor activity, RNA polymerase II-specific / mitochondrial matrix / nuclear speck / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / cell division / protein domain specific binding / centrosome / negative regulation of DNA-templated transcription / synapse / apoptotic process / chromatin binding / chromatin / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / protein kinase binding / negative regulation of transcription by RNA polymerase II / signal transduction
Similarity search - Function
Glucocorticoid receptor / Glucocorticoid receptor / Nuclear receptor coactivator 2 / Nuclear receptor coactivator 2/3, DUF4927 / Domain of unknown function (DUF4927) / 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 ...Glucocorticoid receptor / Glucocorticoid receptor / Nuclear receptor coactivator 2 / Nuclear receptor coactivator 2/3, DUF4927 / Domain of unknown function (DUF4927) / 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-HCY / Glucocorticoid receptor / Nuclear receptor coactivator 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.5 Å
AuthorsHe, Y. / Zhou, X.E. / Tolbert, W.D. / Powell, K. / Melcher, K. / Xu, H.E.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)DK066202 United States
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)DK071662 United States
AAF2010 senior award United States
CitationJournal: Cell Res. / Year: 2014
Title: Structures and mechanism for the design of highly potent glucocorticoids.
Authors: He, Y. / Yi, W. / Suino-Powell, K. / Zhou, X.E. / Tolbert, W.D. / Tang, X. / Yang, J. / Yang, H. / Shi, J. / Hou, L. / Jiang, H. / Melcher, K. / Xu, H.E.
History
DepositionMar 25, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 16, 2014Provider: repository / Type: Initial release
Revision 1.1May 7, 2014Group: Database references
Revision 1.2Jul 16, 2014Group: Database references
Revision 1.3Sep 27, 2017Group: Author supporting evidence / Derived calculations ...Author supporting evidence / Derived calculations / Other / Refinement description / Source and taxonomy / Structure summary
Category: entity_src_gen / pdbx_audit_support ...entity_src_gen / pdbx_audit_support / pdbx_database_status / pdbx_entity_src_syn / pdbx_struct_assembly / pdbx_struct_oper_list / software / struct_keywords
Item: _entity_src_gen.pdbx_alt_source_flag / _pdbx_audit_support.funding_organization ..._entity_src_gen.pdbx_alt_source_flag / _pdbx_audit_support.funding_organization / _pdbx_database_status.pdb_format_compatible / _pdbx_entity_src_syn.pdbx_alt_source_flag / _pdbx_struct_assembly.oligomeric_details / _pdbx_struct_oper_list.symmetry_operation / _struct_keywords.text
Revision 1.4Dec 25, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.5Dec 27, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / refine_hist
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _refine_hist.pdbx_number_atoms_nucleic_acid / _refine_hist.pdbx_number_atoms_protein

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Glucocorticoid receptor
B: Nuclear receptor coactivator 2
C: Glucocorticoid receptor
D: Nuclear receptor coactivator 2
E: Glucocorticoid receptor
F: Nuclear receptor coactivator 2
G: Glucocorticoid receptor
H: Nuclear receptor coactivator 2
I: Glucocorticoid receptor
J: Nuclear receptor coactivator 2
K: Glucocorticoid receptor
L: Nuclear receptor coactivator 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)189,84518
Polymers187,67112
Non-polymers2,1756
Water11,133618
1
A: Glucocorticoid receptor
B: Nuclear receptor coactivator 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,6413
Polymers31,2782
Non-polymers3621
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1900 Å2
ΔGint-9 kcal/mol
Surface area12720 Å2
MethodPISA
2
C: Glucocorticoid receptor
D: Nuclear receptor coactivator 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,6413
Polymers31,2782
Non-polymers3621
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2030 Å2
ΔGint-7 kcal/mol
Surface area13150 Å2
MethodPISA
3
E: Glucocorticoid receptor
F: Nuclear receptor coactivator 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,6413
Polymers31,2782
Non-polymers3621
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1960 Å2
ΔGint-8 kcal/mol
Surface area13080 Å2
MethodPISA
4
G: Glucocorticoid receptor
H: Nuclear receptor coactivator 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,6413
Polymers31,2782
Non-polymers3621
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1940 Å2
ΔGint-6 kcal/mol
Surface area12840 Å2
MethodPISA
5
I: Glucocorticoid receptor
J: Nuclear receptor coactivator 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,6413
Polymers31,2782
Non-polymers3621
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1970 Å2
ΔGint-6 kcal/mol
Surface area13180 Å2
MethodPISA
6
K: Glucocorticoid receptor
L: Nuclear receptor coactivator 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,6413
Polymers31,2782
Non-polymers3621
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2000 Å2
ΔGint-6 kcal/mol
Surface area13100 Å2
MethodPISA
Unit cell
Length a, b, c (Å)220.824, 220.824, 74.198
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number169
Space group name H-MP61

-
Components

#1: Protein
Glucocorticoid receptor / / GR / Nuclear receptor subfamily 3 group C member 1


Mass: 29569.506 Da / Num. of mol.: 6 / Fragment: Ligand binding domain (UNP residues 523-777) / Mutation: F602A, C622Y, T668V, S674T, V675I, E684A, E688A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NR3C1, GRL / Production host: Escherichia coli K-12 (bacteria) / References: UniProt: P04150
#2: Protein/peptide
Nuclear receptor coactivator 2 / / NCoA-2 / Class E basic helix-loop-helix protein 75 / bHLHe75 / Transcriptional intermediary factor 2 / hTIF2


Mass: 1708.931 Da / Num. of mol.: 6
Fragment: SRC2-3 peptide longer version (UNP residues 740-753)
Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q15596
#3: Chemical
ChemComp-HCY / (11alpha,14beta)-11,17,21-trihydroxypregn-4-ene-3,20-dione / CORTISOL / Cortisol


Mass: 362.460 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C21H30O5 / Comment: medication, hormone*YM
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 618 / 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: 2.78 Å3/Da / Density % sol: 55.8 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop / pH: 6.5
Details: 0.1 M imidazole, pH6.5, and 1 M sodium acetate trihydrate. 30% sucrose

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 0.987 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Jul 22, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.987 Å / Relative weight: 1
ReflectionResolution: 2.5→30 Å / Num. obs: 71878 / % possible obs: 100 % / Redundancy: 9 % / Rmerge(I) obs: 0.1 / Net I/σ(I): 19.9

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
HKL-2000data scaling
PDB_EXTRACT3.14data extraction
PHASERphasing
PHENIX1.8.4_1496refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.5→30 Å / SU ML: 0.33 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 30.29 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2755 5583 7.81 %
Rwork0.2457 --
obs0.248 71515 99.67 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 95.73 Å2 / Biso mean: 31.5161 Å2 / Biso min: 4.52 Å2
Refinement stepCycle: final / Resolution: 2.5→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms13074 0 156 618 13848
Biso mean--23.05 29.92 -
Num. residues----1605

+
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