[English] 日本語
Yorodumi
- PDB-4mdd: Crystal Structure of the Glucocorticoid Receptor Bound to a Non-s... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4mdd
TitleCrystal Structure of the Glucocorticoid Receptor Bound to a Non-steroidal Antagonist Reveals Repositioning and Partial Disordering of Activation Function Helix 12
Components
  • Glucocorticoid receptor
  • Nuclear receptor corepressor 1
KeywordsPROTEIN BINDING / nuclear hormone receptor ligand binding domain
Function / homology
Function and homology information


Regulation of NPAS4 gene transcription / Loss of MECP2 binding ability to the NCoR/SMRT complex / nuclear glucocorticoid receptor activity / microglia differentiation / neuroinflammatory response / PTK6 Expression / negative regulation of transcription initiation by RNA polymerase II / steroid hormone binding / negative regulation of androgen receptor signaling pathway / astrocyte differentiation ...Regulation of NPAS4 gene transcription / Loss of MECP2 binding ability to the NCoR/SMRT complex / nuclear glucocorticoid receptor activity / microglia differentiation / neuroinflammatory response / PTK6 Expression / negative regulation of transcription initiation by RNA polymerase II / steroid hormone binding / negative regulation of androgen receptor signaling pathway / astrocyte differentiation / motor behavior / negative regulation of JNK cascade / negative regulation of glycolytic process / nuclear thyroid hormone receptor binding / cellular response to dexamethasone stimulus / cellular response to glucocorticoid stimulus / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / negative regulation of fatty acid metabolic process / cellular response to steroid hormone stimulus / Notch-HLH transcription pathway / locomotor rhythm / transcription repressor complex / histone deacetylase complex / nuclear receptor-mediated steroid hormone signaling pathway / estrogen response element binding / cellular response to transforming growth factor beta stimulus / Regulation of MECP2 expression and activity / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / Nuclear signaling by ERBB4 / core promoter sequence-specific DNA binding / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / spindle assembly / steroid binding / Regulation of lipid metabolism by PPARalpha / RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression / Expression of BMAL (ARNTL), CLOCK, and NPAS2 / negative regulation of miRNA transcription / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / TBP-class protein binding / nuclear receptor binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / SUMOylation of intracellular receptors / Heme signaling / synaptic transmission, glutamatergic / HDACs deacetylate histones / chromosome segregation / PPARA activates gene expression / Transcriptional activation of mitochondrial biogenesis / Cytoprotection by HMOX1 / promoter-specific chromatin binding / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / Hsp90 protein binding / positive regulation of miRNA transcription / DNA-binding transcription repressor activity, RNA polymerase II-specific / mitotic spindle / nuclear receptor activity / NOTCH1 Intracellular Domain Regulates Transcription / spindle / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Activation of anterior HOX genes in hindbrain development during early embryogenesis / histone deacetylase binding / HCMV Early Events / sequence-specific double-stranded DNA binding / Regulation of RUNX2 expression and activity / transcription corepressor activity / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / DNA-binding transcription activator activity, RNA polymerase II-specific / chromatin organization / Potential therapeutics for SARS / RNA polymerase II-specific DNA-binding transcription factor binding / DNA-binding transcription factor activity, RNA polymerase II-specific / nuclear speck / transcription cis-regulatory region binding / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / mitochondrial matrix / cell division / negative regulation of DNA-templated transcription / apoptotic process / centrosome / regulation of transcription by RNA polymerase II / regulation of DNA-templated transcription / synapse / protein kinase binding / chromatin / negative regulation of transcription by RNA polymerase II / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / mitochondrion / DNA-templated transcription / RNA binding / nucleoplasm / zinc ion binding / membrane / identical protein binding / nucleus
Similarity search - Function
Nuclear receptor corepressor 1 N-terminal domain / N-CoR, GPS2-interacting domain / : / G-protein pathway suppressor 2-interacting domain / Glucocorticoid receptor / Glucocorticoid receptor / SANT domain profile. / SANT domain / Myb domain / Myb-like DNA-binding domain ...Nuclear receptor corepressor 1 N-terminal domain / N-CoR, GPS2-interacting domain / : / G-protein pathway suppressor 2-interacting domain / Glucocorticoid receptor / Glucocorticoid receptor / SANT domain profile. / SANT domain / Myb domain / Myb-like DNA-binding domain / : / SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains / SANT/Myb domain / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormone receptor / Homeobox-like domain superfamily / 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
Chem-29M / Nuclear receptor corepressor 1 / Glucocorticoid receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å
AuthorsCoghlan, M.J. / Luz, J.G.
CitationJournal: To be Published
Title: Crystal Structure of the Glucocorticoid Receptor Bound to a Non-steroidal Antagonist Reveals Repositioning and Partial Disordering of Activation Function Helix 12
Authors: Luz, J.G. / Coghlan, M.J.
History
DepositionAug 22, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 3, 2014Provider: repository / Type: Initial release
Revision 1.1Feb 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: Glucocorticoid receptor
B: Glucocorticoid receptor
C: Nuclear receptor corepressor 1
D: Nuclear receptor corepressor 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)63,6186
Polymers62,5984
Non-polymers1,0192
Water2,018112
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7220 Å2
ΔGint-63 kcal/mol
Surface area24070 Å2
MethodPISA
Unit cell
Length a, b, c (Å)72.543, 72.543, 229.472
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: 29667.309 Da / Num. of mol.: 2 / Fragment: unp residues 522-777
Mutation: L525S, L528S, L535A, V538T, F602Y, C638D, E684A, E688A, W712S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NR3C1, GRL / Production host: Escherichia coli (E. coli) / References: UniProt: P04150
#2: Protein/peptide Nuclear receptor corepressor 1 / N-CoR / N-CoR1


Mass: 1631.937 Da / Num. of mol.: 2 / Fragment: unp residues 2260-2274 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: O75376
#3: Chemical ChemComp-29M / N-[2-{[benzyl(methyl)amino]methyl}-3-(4-fluoro-2-methoxyphenyl)-5-(propan-2-yl)-1H-indol-7-yl]methanesulfonamide


Mass: 509.635 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C28H32FN3O3S
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 112 / 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: 55.83 %
Crystal growTemperature: 294 K / Method: vapor diffusion, sitting drop / pH: 7
Details: 100mM Tris HCl plus 6% 1,6 - Hexanediol + 24% PEG 8K, pH 7, VAPOR DIFFUSION, SITTING DROP, temperature 294K

-
Data collection

DiffractionMean temperature: 77 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.97931 Å
DetectorType: RAYONIX MX225HE / Detector: CCD / Date: Feb 15, 2012
RadiationMonochromator: Kohzu HLD-4 Double Crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97931 Å / Relative weight: 1
ReflectionResolution: 2.18→19.8 Å / Num. all: 37462 / Num. obs: 406044 / % possible obs: 99.6 % / Biso Wilson estimate: 51.93 Å2
Reflection shellResolution: 2.18→2.3 Å / % possible all: 100

-
Processing

Software
NameVersionClassification
AMoREphasing
BUSTER2.11.5refinement
d*TREKdata reduction
d*TREKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.4→19.8 Å / Cor.coef. Fo:Fc: 0.9222 / Cor.coef. Fo:Fc free: 0.8948 / SU R Cruickshank DPI: 0.315 / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.2584 870 3.09 %RANDOM
Rwork0.2208 ---
obs0.222 28177 99.61 %-
Displacement parametersBiso mean: 54.15 Å2
Baniso -1Baniso -2Baniso -3
1--1.1668 Å20 Å20 Å2
2---1.1668 Å20 Å2
3---2.3337 Å2
Refine analyzeLuzzati coordinate error obs: 0.328 Å
Refinement stepCycle: LAST / Resolution: 2.4→19.8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3957 0 72 112 4141
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0094112HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.075560HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1455SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes97HARMONIC2
X-RAY DIFFRACTIONt_gen_planes593HARMONIC5
X-RAY DIFFRACTIONt_it4112HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.76
X-RAY DIFFRACTIONt_other_torsion18.16
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion523SEMIHARMONIC5
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_contact4822SEMIHARMONIC4
LS refinement shellResolution: 2.4→2.49 Å / Total num. of bins used: 14
RfactorNum. reflection% reflection
Rfree0.2946 86 2.92 %
Rwork0.2361 2856 -
all0.2377 2942 -
obs--99.61 %

+
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