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Yorodumi- PDB-6w9h: SUBSTITUTED BENZYLOXYTRICYCLIC COMPOUNDS AS RETINOIC ACID-RELATED... -
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-Basic information
Entry | Database: PDB / ID: 6w9h | ||||||
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Title | SUBSTITUTED BENZYLOXYTRICYCLIC COMPOUNDS AS RETINOIC ACID-RELATED ORPHAN RECEPTOR GAMMA T AGONISTS | ||||||
Components | Nuclear receptor ROR-gamma, Steroid receptor coactivator 1 fusion | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / RORGT / NUCLEAR HORMONE RECEPTOR / LIGAND-BINDING DOMAIN / INVE AGONIST / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX / TRANSFERASE | ||||||
Function / homology | Function and homology information T-helper 17 cell differentiation / ligand-activated transcription factor activity / cellular response to sterol / regulation of steroid metabolic process / Peyer's patch development / T-helper cell differentiation / positive regulation of circadian rhythm / oxysterol binding / RUNX3 Regulates Immune Response and Cell Migration / labyrinthine layer morphogenesis ...T-helper 17 cell differentiation / ligand-activated transcription factor activity / cellular response to sterol / regulation of steroid metabolic process / Peyer's patch development / T-helper cell differentiation / positive regulation of circadian rhythm / oxysterol binding / RUNX3 Regulates Immune Response and Cell Migration / labyrinthine layer morphogenesis / negative regulation of thymocyte apoptotic process / regulation of thyroid hormone mediated signaling pathway / positive regulation of transcription from RNA polymerase II promoter by galactose / positive regulation of female receptivity / regulation of fat cell differentiation / hypothalamus development / male mating behavior / NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis / estrous cycle / cellular response to Thyroglobulin triiodothyronine / regulation of glucose metabolic process / Synthesis of bile acids and bile salts / lymph node development / adipose tissue development / Endogenous sterols / Synthesis of bile acids and bile salts via 27-hydroxycholesterol / Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol / nuclear retinoid X receptor binding / response to retinoic acid / histone acetyltransferase activity / regulation of cellular response to insulin stimulus / Recycling of bile acids and salts / histone acetyltransferase / 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 / lactation / positive regulation of neuron differentiation / Regulation of lipid metabolism by PPARalpha / xenobiotic metabolic process / cerebellum development / BMAL1:CLOCK,NPAS2 activates circadian gene expression / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / nuclear receptor coactivator activity / response to progesterone / nuclear estrogen receptor binding / nuclear receptor binding / hippocampus development / RNA polymerase II transcription regulatory region sequence-specific DNA binding / circadian regulation of gene expression / Heme signaling / mRNA transcription by RNA polymerase II / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / Cytoprotection by HMOX1 / cerebral cortex development / DNA-binding transcription repressor activity, RNA polymerase II-specific / Transcriptional regulation of white adipocyte differentiation / Nuclear Receptor transcription pathway / RNA polymerase II transcription regulator complex / male gonad development / nuclear receptor activity / Circadian Clock / sequence-specific double-stranded DNA binding / response to estradiol / HATs acetylate histones / Interleukin-4 and Interleukin-13 signaling / Estrogen-dependent gene expression / transcription regulator complex / transcription coactivator activity / nuclear body / protein dimerization activity / DNA-binding transcription factor activity, RNA polymerase II-specific / positive regulation of apoptotic process / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / chromatin binding / chromatin / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein-containing complex / zinc ion binding / nucleoplasm / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.995 Å | ||||||
Authors | Sack, J.S. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2020 Title: Substituted benzyloxytricyclic compounds as retinoic acid-related orphan receptor gamma t (ROR gamma t) agonists. Authors: Harikrishnan, L.S. / Gill, P. / Kamau, M.G. / Qin, L.Y. / Ruan, Z. / O'Malley, D. / Huynh, T. / Stachura, S. / Cavallaro, C.L. / Lu, Z. / J-W Duan, J. / Weigelt, C.A. / Sack, J.S. / Ruzanov, ...Authors: Harikrishnan, L.S. / Gill, P. / Kamau, M.G. / Qin, L.Y. / Ruan, Z. / O'Malley, D. / Huynh, T. / Stachura, S. / Cavallaro, C.L. / Lu, Z. / J-W Duan, J. / Weigelt, C.A. / Sack, J.S. / Ruzanov, M. / Khan, J. / Gururajan, M. / Wong, J.J. / Huang, Y. / Yarde, M. / Li, Z. / Chen, C. / Sun, H. / Borowski, V. / Murtaza, A. / Fink, B.E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6w9h.cif.gz | 72.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6w9h.ent.gz | 50 KB | Display | PDB format |
PDBx/mmJSON format | 6w9h.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w9/6w9h ftp://data.pdbj.org/pub/pdb/validation_reports/w9/6w9h | HTTPS FTP |
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-Related structure data
Related structure data | 6w9iC 6xaeC 6vqfS 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: 32886.922 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RORC, NR1F3, RORG, RZRG, NCOA1, BHLHE74, SRC1 / Production host: Escherichia coli (E. coli) References: UniProt: P51449, UniProt: Q15788, histone acetyltransferase |
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#2: Chemical | ChemComp-TKJ / |
#3: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.29 Å3/Da / Density % sol: 46.21 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, hanging drop Details: protein at 8-10mg/ml, with 0.2M MgCl2, 22% PEG3350, 0.1M Bis-Tris pH 5.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 16, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.995→57.39 Å / Num. obs: 15332 / % possible obs: 71.9 % / Redundancy: 12.3 % / Biso Wilson estimate: 31.01 Å2 / Rmerge(I) obs: 0.159 / Net I/σ(I): 12.7 |
Reflection shell | Resolution: 2→2.15 Å / Redundancy: 10.9 % / Rmerge(I) obs: 1.945 / Mean I/σ(I) obs: 1.4 / Num. unique obs: 1000 / % possible all: 18.1 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6vqf Resolution: 1.995→57.39 Å / Cor.coef. Fo:Fc: 0.934 / Cor.coef. Fo:Fc free: 0.874 / SU R Cruickshank DPI: 0.257 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.284 / SU Rfree Blow DPI: 0.224 / SU Rfree Cruickshank DPI: 0.217
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Displacement parameters | Biso max: 83.85 Å2 / Biso mean: 31.78 Å2 / Biso min: 15.43 Å2
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Refine analyze | Luzzati coordinate error obs: 0.28 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.995→57.39 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2→2.1 Å / Rfactor Rfree error: 0
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