[English] 日本語
Yorodumi
- PDB-6el9: Glucocorticoid Receptor in complex with AZD9567 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6el9
TitleGlucocorticoid Receptor in complex with AZD9567
Components
  • Glucocorticoid receptor
  • Nuclear receptor coactivator 2
KeywordsSIGNALING PROTEIN / Glucocorticoid receptor / nuclear hormone receptor / steroid receptor / ligand complex / peptide 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 / neuroinflammatory response / glucocorticoid metabolic process / mammary gland duct morphogenesis / microglia differentiation / maternal behavior ...Regulation of NPAS4 gene transcription / regulation of glucocorticoid biosynthetic process / nuclear glucocorticoid receptor activity / steroid hormone binding / PTK6 Expression / neuroinflammatory response / glucocorticoid metabolic process / mammary gland duct morphogenesis / microglia differentiation / maternal behavior / astrocyte differentiation / cellular response to glucocorticoid stimulus / motor behavior / adrenal gland development / cellular response to steroid hormone stimulus / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / regulation of gluconeogenesis / 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 / nuclear receptor-mediated steroid hormone signaling pathway / core promoter sequence-specific DNA binding / Recycling of bile acids and salts / cellular response to transforming growth factor beta stimulus / cellular response to hormone stimulus / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / positive regulation of adipose tissue development / RORA activates gene expression / peroxisome proliferator activated receptor signaling pathway / steroid binding / Regulation of lipid metabolism by PPARalpha / TBP-class protein binding / regulation of cellular response to insulin stimulus / cellular response to dexamethasone stimulus / BMAL1:CLOCK,NPAS2 activates circadian gene expression / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / nuclear receptor coactivator activity / synaptic transmission, glutamatergic / chromosome segregation / response to progesterone / nuclear receptor binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / circadian regulation of gene expression / SUMOylation of intracellular receptors / Heme signaling / Hsp90 protein binding / 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 / DNA-binding transcription repressor activity, RNA polymerase II-specific / positive regulation of miRNA transcription / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / spindle / RNA polymerase II transcription regulator complex / positive regulation of neuron apoptotic process / nuclear receptor activity / Regulation of RUNX2 expression and activity / sequence-specific double-stranded DNA binding / Circadian Clock / chromatin organization / HATs acetylate histones / gene expression / DNA-binding transcription activator activity, RNA polymerase II-specific / Estrogen-dependent gene expression / transcription regulator complex / Potential therapeutics for SARS / transcription coactivator activity / nuclear body / protein dimerization activity / DNA-binding transcription factor activity, RNA polymerase II-specific / nuclear speck / mitochondrial matrix / DNA-binding transcription factor activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / protein domain specific binding / cell division / negative regulation of DNA-templated transcription / centrosome / chromatin binding / synapse / regulation of DNA-templated transcription / chromatin / regulation of transcription by RNA polymerase II / apoptotic process / protein kinase binding / negative regulation of transcription by RNA polymerase II / signal transduction / positive regulation of transcription by RNA polymerase II
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 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 / 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-B9W / Glucocorticoid receptor / Nuclear receptor coactivator 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.19 Å
AuthorsEdman, K. / Wissler, L.
CitationJournal: J. Med. Chem. / Year: 2018
Title: Discovery of a Novel Oral Glucocorticoid Receptor Modulator (AZD9567) with Improved Side Effect Profile.
Authors: Ripa, L. / Edman, K. / Dearman, M. / Edenro, G. / Hendrickx, R. / Ullah, V. / Chang, H.F. / Lepisto, M. / Chapman, D. / Geschwindner, S. / Wissler, L. / Svanberg, P. / Lawitz, K. / Malmberg, ...Authors: Ripa, L. / Edman, K. / Dearman, M. / Edenro, G. / Hendrickx, R. / Ullah, V. / Chang, H.F. / Lepisto, M. / Chapman, D. / Geschwindner, S. / Wissler, L. / Svanberg, P. / Lawitz, K. / Malmberg, J. / Nikitidis, A. / Olsson, R.I. / Bird, J. / Llinas, A. / Hegelund-Myrback, T. / Berger, M. / Thorne, P. / Harrison, R. / Kohler, C. / Drmota, T.
History
DepositionSep 28, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 21, 2018Provider: repository / Type: Initial release
Revision 1.1Mar 21, 2018Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2Jan 17, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Glucocorticoid receptor
B: Nuclear receptor coactivator 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,2964
Polymers33,7392
Non-polymers5572
Water1,13563
1


  • Idetical with deposited unit
  • defined by software
  • Evidence: Binding of peptide measured by surface plasmon resonance, binding of ligand measured in binding assay
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1480 Å2
ΔGint-4 kcal/mol
Surface area12420 Å2
MethodPISA
Unit cell
Length a, b, c (Å)84.523, 84.523, 105.718
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number154
Space group name H-MP3221

-
Components

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


Mass: 32029.971 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: Expression and crystallisation mutants: N517D, V571M, F602S, C638D, E684A, W712S
Source: (gene. exp.) Homo sapiens (human) / Gene: NR3C1, GRL / Production host: Trichoplusia ni (cabbage looper) / 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.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q15596
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#4: Chemical ChemComp-B9W / 2,2-bis(fluoranyl)-~{N}-[(1~{R},2~{S})-3-methyl-1-[1-(1-methyl-6-oxidanylidene-pyridin-3-yl)indazol-5-yl]oxy-1-phenyl-butan-2-yl]propanamide


Mass: 494.533 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C27H28F2N4O3
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 63 / 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: 3.23 Å3/Da / Density % sol: 61.93 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop
Details: 8-10% PEG8000, 10-19% Ethylene Glycol, 0.1 M HEPES pH 7.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.976 Å
DetectorType: DECTRIS PILATUS 12M / Detector: PIXEL / Date: Feb 3, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.976 Å / Relative weight: 1
ReflectionResolution: 2.19→105.72 Å / Num. obs: 22910 / % possible obs: 100 % / Redundancy: 9.7 % / Biso Wilson estimate: 57.04 Å2 / Rpim(I) all: 0.032 / Net I/σ(I): 17.4
Reflection shellResolution: 2.19→2.31 Å / Mean I/σ(I) obs: 2.6 / Rpim(I) all: 0.358

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
XDSdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4csj

4csj


Resolution: 2.19→60.18 Å / Cor.coef. Fo:Fc: 0.934 / Cor.coef. Fo:Fc free: 0.895 / SU R Cruickshank DPI: 0.169 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.169 / SU Rfree Blow DPI: 0.152 / SU Rfree Cruickshank DPI: 0.152
RfactorNum. reflection% reflectionSelection details
Rfree0.224 1174 5.13 %RANDOM
Rwork0.194 ---
obs0.195 22879 99.5 %-
Displacement parametersBiso mean: 72.7 Å2
Baniso -1Baniso -2Baniso -3
1--9.7351 Å20 Å20 Å2
2---9.7351 Å20 Å2
3---19.4702 Å2
Refine analyzeLuzzati coordinate error obs: 0.28 Å
Refinement stepCycle: 1 / Resolution: 2.19→60.18 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2115 0 40 63 2218
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.012199HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.022972HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d785SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes57HARMONIC2
X-RAY DIFFRACTIONt_gen_planes314HARMONIC5
X-RAY DIFFRACTIONt_it2199HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.55
X-RAY DIFFRACTIONt_other_torsion16.81
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion279SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact2563SEMIHARMONIC4
LS refinement shellResolution: 2.19→2.3 Å / Total num. of bins used: 11
RfactorNum. reflection% reflection
Rfree0.2726 147 5.06 %
Rwork0.2215 2757 -
all0.2241 2904 -
obs--96.1 %
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)
13.2480.03261.6141.0435-0.38253.3891-0.2882-0.24390.40360.01230.00610.0573-0.5605-0.44910.2821-0.15110.1262-0.0439-0.2766-0.0923-0.2855-34.3217-11.78213.1453
27.4784-1.8561-3.67554.7014-1.13590.5985-0.08530.11380.09970.00450.0779-0.0662-0.02660.13270.0075-0.06380.02690.0416-0.0699-0.0467-0.0426-15.7698-18.7673-1.5432
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ A|* }
2X-RAY DIFFRACTION2{ B|* }

+
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