+Open data
-Basic information
Entry | Database: PDB / ID: 6el6 | ||||||
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Title | Glucocorticoid Receptor in complex with compound 4 | ||||||
Components |
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Keywords | SIGNALING 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 / 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 / estrogen response element binding / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / 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 / SUMOylation of transcription cofactors / nuclear receptor coactivator activity / 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 / SUMOylation of intracellular receptors / Heme signaling / 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 / Regulation of RUNX2 expression and activity / positive regulation of neuron apoptotic process / 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 | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å | ||||||
Authors | Edman, K. / Wissler, L. | ||||||
Citation | Journal: 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 |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6el6.cif.gz | 125.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6el6.ent.gz | 96.2 KB | Display | PDB format |
PDBx/mmJSON format | 6el6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/el/6el6 ftp://data.pdbj.org/pub/pdb/validation_reports/el/6el6 | HTTPS FTP |
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-Related structure data
Related structure data | 6el7C 6el9C 4csjS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 32187.139 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Mutants included for protein expression and crystallisation: N517D, V571M, F602S, C638D Source: (gene. exp.) Homo sapiens (human) / Gene: NR3C1, GRL / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P04150 |
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#2: Protein/peptide | Mass: 1708.931 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q15596 |
#3: Chemical | ChemComp-EDO / |
#4: Chemical | ChemComp-B9Q / ~{ |
#5: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.27 Å3/Da / Density % sol: 62.38 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop Details: 8-10% PEG8000, 10-19% Ethylene Glycol, 0.1 M HEPES pH 7.5 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID23-2 / Wavelength: 0.873 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 18, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.873 Å / Relative weight: 1 |
Reflection | Resolution: 2.4→43.1 Å / Num. obs: 17764 / % possible obs: 99.6 % / Redundancy: 5.6 % / Biso Wilson estimate: 45.2 Å2 / Rpim(I) all: 0.108 / Net I/σ(I): 5.6 |
Reflection shell | Resolution: 2.4→2.46 Å / Redundancy: 5.7 % / Mean I/σ(I) obs: 1.7 / Num. unique obs: 1293 / Rpim(I) all: 0.539 / % possible all: 99.3 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4csj Resolution: 2.4→43.1 Å / Cor.coef. Fo:Fc: 0.892 / Cor.coef. Fo:Fc free: 0.851 / SU R Cruickshank DPI: 0.303 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.312 / SU Rfree Blow DPI: 0.242 / SU Rfree Cruickshank DPI: 0.241
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Displacement parameters | Biso mean: 42.56 Å2
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Refine analyze | Luzzati coordinate error obs: 0.36 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.4→43.1 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.4→2.54 Å / Total num. of bins used: 9
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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