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Yorodumi- PDB-4m8h: CRYSTAL STRUCTURE OF HUMAN RETINOID X RECEPTOR ALPHA-LIGAND BINDI... -
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-Basic information
Entry | Database: PDB / ID: 4m8h | ||||||
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Title | CRYSTAL STRUCTURE OF HUMAN RETINOID X RECEPTOR ALPHA-LIGAND BINDING DOMAIN COMPLEX WITH (R)4-METHYL 9cUAB30 AND COACTIVATOR PEPTIDE GRIP-1 | ||||||
Components |
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Keywords | TRANSCRIPTION / ANTIPARALLEL SANDWICH / LIGAND BINDING / COACTIVATOR BINDING / DIMERIZATION / ACTIVATION FUNCTION / nuclear receptors / ligand binding domain / ligand binding pocket / coactivator binding site / cancer / (R)4-Methyl UAB30 [(2E / 4E / 6Z / 8E)-8-[(4'R)methyl-3' / 4'-dihydro-1'(2'H)-naphthalen-1'-ylidene]-3 / 7-dimethyl-2 / 4 / 6-octatrienoic Acid] | ||||||
Function / homology | Function and homology information positive regulation of transporter activity / retinoic acid-responsive element binding / NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis / NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose / NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake / positive regulation of thyroid hormone receptor signaling pathway / NR1H2 & NR1H3 regulate gene expression linked to lipogenesis / Carnitine metabolism / ion binding / Regulation of pyruvate dehydrogenase (PDH) complex ...positive regulation of transporter activity / retinoic acid-responsive element binding / NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis / NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose / NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake / positive regulation of thyroid hormone receptor signaling pathway / NR1H2 & NR1H3 regulate gene expression linked to lipogenesis / Carnitine metabolism / ion binding / Regulation of pyruvate dehydrogenase (PDH) complex / retinoic acid binding / positive regulation of vitamin D receptor signaling pathway / nuclear vitamin D receptor binding / Signaling by Retinoic Acid / DNA binding domain binding / nuclear steroid receptor activity / RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / LBD domain binding / 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 / positive regulation of cholesterol efflux / retinoic acid receptor signaling pathway / Endogenous sterols / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / positive regulation of bone mineralization / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / response to retinoic acid / regulation of cellular response to insulin stimulus / Recycling of bile acids and salts / cellular response to hormone stimulus / NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux / positive regulation of adipose tissue development / peroxisome proliferator activated receptor signaling pathway / RORA activates gene expression / Regulation of lipid metabolism by PPARalpha / hormone-mediated signaling pathway / BMAL1:CLOCK,NPAS2 activates circadian gene expression / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / nuclear receptor coactivator activity / transcription coregulator binding / response to progesterone / nuclear receptor binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / peptide 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 / Transcriptional regulation of white adipocyte differentiation / Activation of anterior HOX genes in hindbrain development during early embryogenesis / Nuclear Receptor transcription pathway / Transcriptional regulation of granulopoiesis / RNA polymerase II transcription regulator complex / nuclear receptor activity / sequence-specific double-stranded DNA binding / Circadian Clock / HATs acetylate histones / double-stranded DNA binding / Estrogen-dependent gene expression / transcription regulator complex / sequence-specific DNA binding / transcription coactivator activity / cell differentiation / receptor complex / nuclear body / protein dimerization activity / transcription cis-regulatory region binding / DNA-binding transcription factor activity, RNA polymerase II-specific / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / protein domain specific binding / chromatin binding / regulation of DNA-templated transcription / chromatin / positive regulation of DNA-templated transcription / enzyme binding / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein-containing complex / mitochondrion / zinc ion binding / nucleoplasm / identical protein binding / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.2 Å | ||||||
Authors | Xia, G. / Smith, C.D. / Muccio, D.D. | ||||||
Citation | Journal: Bioorg.Med.Chem. / Year: 2014 Title: Methyl-substituted conformationally constrained rexinoid agonists for the retinoid X receptors demonstrate improved efficacy for cancer therapy and prevention. Authors: Desphande, A. / Xia, G. / Boerma, L.J. / Vines, K.K. / Atigadda, V.R. / Lobo-Ruppert, S. / Grubbs, C.J. / Moeinpour, F.L. / Smith, C.D. / Christov, K. / Brouillette, W.J. / Muccio, D.D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4m8h.cif.gz | 62.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4m8h.ent.gz | 44.4 KB | Display | PDB format |
PDBx/mmJSON format | 4m8h.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4m8h_validation.pdf.gz | 705.7 KB | Display | wwPDB validaton report |
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Full document | 4m8h_full_validation.pdf.gz | 710 KB | Display | |
Data in XML | 4m8h_validation.xml.gz | 12.8 KB | Display | |
Data in CIF | 4m8h_validation.cif.gz | 17.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/m8/4m8h ftp://data.pdbj.org/pub/pdb/validation_reports/m8/4m8h | HTTPS FTP |
-Related structure data
Related structure data | 4m8eC 3oapS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 25897.021 Da / Num. of mol.: 1 / Fragment: HRXRALPHA-LBD, UNP RESIDUES 228-458 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Strain: P19793 / Gene: NR2B1, RXRA / Production host: Escherichia coli (E. coli) / References: UniProt: P19793 |
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#2: Protein/peptide | Mass: 1405.710 Da / Num. of mol.: 1 / Fragment: GRIP-1, UNP RESIDUES 686-696 / Source method: obtained synthetically / Details: GRIP-1 from AnaSpec. Inc / Source: (synth.) Homo sapiens (human) / References: UniProt: Q15596 |
#3: Chemical | ChemComp-R4M / ( |
#4: 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: 2.26 Å3/Da / Density % sol: 45.7 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 4-20% PEG4000, 4-16% GLYCEROL, 0.1M BIS-TRIS, PH7.0, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 295K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||
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Diffraction source | Source: ROTATING ANODE / Site: APS / Beamline: 22-ID / Type: OTHER / Wavelength: 1.5418 / Wavelength: 1.315 Å | |||||||||
Detector | Type: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Feb 19, 2009 | |||||||||
Radiation | Monochromator: graphite / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||
Radiation wavelength |
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Reflection | Resolution: 2.2→29.3 Å / Num. all: 34390 / Num. obs: 12013 / % possible obs: 91.8 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Redundancy: 2.86 % / Rmerge(I) obs: 0.078 / Rsym value: 0.218 / Net I/σ(I): 11.2 | |||||||||
Reflection shell | Resolution: 2.2→2.28 Å / Redundancy: 2.66 % / Num. unique all: 1263 / % possible all: 94.5 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3OAP Resolution: 2.2→29.3 Å / σ(F): 2 / σ(I): 2 / Stereochemistry target values: Engh & Huber
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Solvent computation | Bsol: 66.66 Å2 | |||||||||||||||||||||||||
Displacement parameters | Biso mean: 30.85 Å2
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Refinement step | Cycle: LAST / Resolution: 2.2→29.3 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.2→2.28 Å / Num. reflection Rwork: 457 / Total num. of bins used: 30 | |||||||||||||||||||||||||
Xplor file |
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