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Yorodumi- PDB-6q7a: RORCVAR2 (RORGT, 264-499) IN COMPLEX WITH COMPOUND 4 AT 2.2A: Ide... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6q7a | ||||||
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Title | RORCVAR2 (RORGT, 264-499) IN COMPLEX WITH COMPOUND 4 AT 2.2A: Identification of N-aryl imidazoles as potent and selective RORgt inhibitors | ||||||
Components | Nuclear receptor ROR-gamma | ||||||
Keywords | TRANSCRIPTION / NUCLEAR HORMONE RECEPTOR / LIGAND-BINDING DOMAIN / INVERSE AGONIST | ||||||
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 / negative regulation of thymocyte apoptotic process ...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 / negative regulation of thymocyte apoptotic process / regulation of fat cell differentiation / regulation of glucose metabolic process / lymph node development / adipose tissue development / xenobiotic metabolic process / circadian regulation of gene expression / DNA-binding transcription repressor activity, RNA polymerase II-specific / Nuclear Receptor transcription pathway / nuclear receptor activity / sequence-specific double-stranded DNA binding / Interleukin-4 and Interleukin-13 signaling / nuclear body / DNA-binding transcription factor activity, RNA polymerase II-specific / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / chromatin / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / zinc ion binding / nucleoplasm / nucleus Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.2 Å | ||||||
Authors | Kallen, J. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2019 Title: Structure-Based and Property-Driven Optimization ofN-Aryl Imidazoles toward Potent and Selective Oral ROR gamma t Inhibitors. Authors: Hoegenauer, K. / Kallen, J. / Jimenez-Nunez, E. / Strang, R. / Ertl, P. / Cooke, N.G. / Hintermann, S. / Voegtle, M. / Betschart, C. / McKay, D.J.J. / Wagner, J. / Ottl, J. / Beerli, C. / ...Authors: Hoegenauer, K. / Kallen, J. / Jimenez-Nunez, E. / Strang, R. / Ertl, P. / Cooke, N.G. / Hintermann, S. / Voegtle, M. / Betschart, C. / McKay, D.J.J. / Wagner, J. / Ottl, J. / Beerli, C. / Billich, A. / Dawson, J. / Kaupmann, K. / Streiff, M. / Gobeau, N. / Harlfinger, S. / Stringer, R. / Guntermann, C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6q7a.cif.gz | 63.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6q7a.ent.gz | 45 KB | Display | PDB format |
PDBx/mmJSON format | 6q7a.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/q7/6q7a ftp://data.pdbj.org/pub/pdb/validation_reports/q7/6q7a | HTTPS FTP |
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-Related structure data
Related structure data | 6q6mC 6q6oSC 6q7hC C: citing same article (ref.) S: Starting model for refinement |
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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: 27629.943 Da / Num. of mol.: 1 / Fragment: C-terminal domain, ligand binding domain / Mutation: C455S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RORC, NR1F3, RORG, RZRG / Plasmid: pET28-derived vector / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: P51449 |
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#2: Chemical | ChemComp-HKZ / |
#3: 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: 3.54 Å3/Da / Density % sol: 65.21 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 8.8 Details: 0.5% PEG MME 5k (w/v), 0.4M KNa Tartrate, 0.1M TRIS |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1.0015 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 19, 2010 |
Radiation | Monochromator: SI 111 channel / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.0015 Å / Relative weight: 1 |
Reflection | Resolution: 2.2→19.89 Å / Num. obs: 20861 / % possible obs: 99.8 % / Redundancy: 16.5 % / Biso Wilson estimate: 49.3 Å2 / Rmerge(I) obs: 0.049 / Rpim(I) all: 0.044 / Rrim(I) all: 0.05 / Net I/σ(I): 39.8 |
Reflection shell | Resolution: 2.2→2.256 Å / Redundancy: 16.8 % / Rmerge(I) obs: 0.595 / Mean I/σ(I) obs: 5.7 / Rpim(I) all: 0.281 / Rrim(I) all: 0.613 / % possible all: 100 |
-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6Q6O Resolution: 2.2→19.89 Å / Cor.coef. Fo:Fc: 0.934 / Cor.coef. Fo:Fc free: 0.919 / SU B: 4.587 / SU ML: 0.116 / SU R Cruickshank DPI: 0.2156 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.216 / ESU R Free: 0.177 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | |||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 76.23 Å2 / Biso mean: 46.824 Å2 / Biso min: 29.15 Å2
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Refinement step | Cycle: final / Resolution: 2.2→19.89 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.2→2.256 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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