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Yorodumi- PDB-6yqo: Crystal structure of the first bromodomain of human BRD4 in compl... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6yqo | ||||||
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Title | Crystal structure of the first bromodomain of human BRD4 in complex with the dual inhibitor TW12 | ||||||
Components | Bromodomain-containing protein 4BRD4 | ||||||
Keywords | GENE REGULATION / bromodomain / BRD4(BD1) / dual bromodomain HDAC inhibitor / structural genomics consortium / SGC | ||||||
Function / homology | Function and homology information RNA polymerase II C-terminal domain binding / negative regulation of DNA damage checkpoint / P-TEFb complex binding / negative regulation by host of viral transcription / positive regulation of T-helper 17 cell lineage commitment / positive regulation of G2/M transition of mitotic cell cycle / histone reader activity / RNA polymerase II CTD heptapeptide repeat kinase activity / condensed nuclear chromosome / positive regulation of transcription elongation by RNA polymerase II ...RNA polymerase II C-terminal domain binding / negative regulation of DNA damage checkpoint / P-TEFb complex binding / negative regulation by host of viral transcription / positive regulation of T-helper 17 cell lineage commitment / positive regulation of G2/M transition of mitotic cell cycle / histone reader activity / RNA polymerase II CTD heptapeptide repeat kinase activity / condensed nuclear chromosome / positive regulation of transcription elongation by RNA polymerase II / transcription coregulator activity / lysine-acetylated histone binding / p53 binding / chromosome / regulation of inflammatory response / positive regulation of canonical NF-kappaB signal transduction / Potential therapeutics for SARS / transcription coactivator activity / transcription cis-regulatory region binding / chromatin remodeling / DNA damage response / chromatin binding / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / enzyme binding / positive regulation of transcription by RNA polymerase II / nucleoplasm / nucleus Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.07 Å | ||||||
Authors | Joerger, A.C. / Balourdas, D.I. / Weiser, T. / Chatterjee, D. / Knapp, S. / Structural Genomics Consortium (SGC) | ||||||
Citation | Journal: Int.J.Cancer / Year: 2020 Title: Characterization of a dual BET/HDAC inhibitor for treatment of pancreatic ductal adenocarcinoma. Authors: Zhang, X. / Zegar, T. / Weiser, T. / Hamdan, F.H. / Berger, B.T. / Lucas, R. / Balourdas, D.I. / Ladigan, S. / Cheung, P.F. / Liffers, S.T. / Trajkovic-Arsic, M. / Scheffler, B. / Joerger, A. ...Authors: Zhang, X. / Zegar, T. / Weiser, T. / Hamdan, F.H. / Berger, B.T. / Lucas, R. / Balourdas, D.I. / Ladigan, S. / Cheung, P.F. / Liffers, S.T. / Trajkovic-Arsic, M. / Scheffler, B. / Joerger, A.C. / Hahn, S.A. / Johnsen, S.A. / Knapp, S. / Siveke, J.T. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6yqo.cif.gz | 90.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6yqo.ent.gz | 56.1 KB | Display | PDB format |
PDBx/mmJSON format | 6yqo.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yq/6yqo ftp://data.pdbj.org/pub/pdb/validation_reports/yq/6yqo | HTTPS FTP |
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-Related structure data
Related structure data | 6yqnC 6yqpC 3mxfS 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: 15099.380 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Production host: Escherichia coli (E. coli) / References: UniProt: O60885 | ||||||
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#2: Chemical | #3: Chemical | ChemComp-P8Q / ( | #4: 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: 2.14 Å3/Da / Density % sol: 42.57 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop Details: Protein solution: 10 mg/ml in 10 mM HEPES, pH 7.5, 150 mM NaCl, 0.5 mM TCEP, and 5% glycerol. 50 mM stock solution of TW12 in DMSO added to give a final inhibitor concentration 1.5 mM. ...Details: Protein solution: 10 mg/ml in 10 mM HEPES, pH 7.5, 150 mM NaCl, 0.5 mM TCEP, and 5% glycerol. 50 mM stock solution of TW12 in DMSO added to give a final inhibitor concentration 1.5 mM. Reservoir buffer: 24% PEG 3350, 0.1 M sodium formate, 15% ethylene glycol and 0.1 M bis-Tris-propane pH 7.3. Ratio protein/reservoir solution = 2:1 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID30B / Wavelength: 0.70848 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Nov 30, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.70848 Å / Relative weight: 1 |
Reflection | Resolution: 1.07→44.29 Å / Num. obs: 57949 / % possible obs: 99.8 % / Redundancy: 10.6 % / Biso Wilson estimate: 9.56225658876 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.079 / Net I/σ(I): 14.3 |
Reflection shell | Resolution: 1.07→1.09 Å / Redundancy: 10.9 % / Rmerge(I) obs: 0.742 / Mean I/σ(I) obs: 3 / Num. unique obs: 2884 / CC1/2: 0.889 / % possible all: 99 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 3mxf Resolution: 1.07→39.3 Å / SU ML: 0.0838345378863 / Cross valid method: FREE R-VALUE / σ(F): 1.33483533151 / Phase error: 18.4419275313
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 13.8563898236 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.07→39.3 Å
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Refine LS restraints |
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LS refinement shell |
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