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Yorodumi- PDB-6fsy: Crystal Structure of the first bromodomain of human BRD4 in compl... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6fsy | ||||||
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Title | Crystal Structure of the first bromodomain of human BRD4 in complex with a 3,5-dimethylisoxazol ligand | ||||||
Components | Bromodomain-containing protein 4 | ||||||
Keywords | TRANSCRIPTION / Bromodomain / ligand / isoxazole / Structural Genomics / 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 / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.34 Å | ||||||
Authors | Filippakopoulos, P. / Picaud, S. / Conway, S.J. / Pike, A.C.W. / Krojer, T. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Structural Genomics Consortium (SGC) | ||||||
Funding support | United Kingdom, 1items
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Citation | Journal: Bioorg.Med.Chem. / Year: 2018 Title: BET bromodomain ligands: Probing the WPF shelf to improve BRD4 bromodomain affinity and metabolic stability. Authors: Jennings, L.E. / Schiedel, M. / Hewings, D.S. / Picaud, S. / Laurin, C.M.C. / Bruno, P.A. / Bluck, J.P. / Scorah, A.R. / See, L. / Reynolds, J.K. / Moroglu, M. / Mistry, I.N. / Hicks, A. / ...Authors: Jennings, L.E. / Schiedel, M. / Hewings, D.S. / Picaud, S. / Laurin, C.M.C. / Bruno, P.A. / Bluck, J.P. / Scorah, A.R. / See, L. / Reynolds, J.K. / Moroglu, M. / Mistry, I.N. / Hicks, A. / Guzanov, P. / Clayton, J. / Evans, C.N.G. / Stazi, G. / Biggin, P.C. / Mapp, A.K. / Hammond, E.M. / Humphreys, P.G. / Filippakopoulos, P. / Conway, S.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6fsy.cif.gz | 76.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6fsy.ent.gz | 55.1 KB | Display | PDB format |
PDBx/mmJSON format | 6fsy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fs/6fsy ftp://data.pdbj.org/pub/pdb/validation_reports/fs/6fsy | HTTPS FTP |
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-Related structure data
Related structure data | 6ft3C 6ft4C 2grcS 2oo1S 2ossS 2ouoS 3d7cS 3daiS 3dwyS 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 / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): R3 / References: UniProt: O60885 | ||||
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#2: Chemical | #3: Chemical | ChemComp-E5Q / | #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: 2.17 Å3/Da / Density % sol: 43.38 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 5.5 / Details: 20 % PEG 3350 and 0.1 M citrate pH 5.5 |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.96861 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Dec 18, 2017 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.96861 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.338→29.22 Å / Num. obs: 30364 / % possible obs: 99.7 % / Redundancy: 6.2 % / Rmerge(I) obs: 0.078 / Rpim(I) all: 0.034 / Rrim(I) all: 0.085 / Rsym value: 0.078 / Net I/av σ(I): 4.4 / Net I/σ(I): 11.3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR | Model details: Phaser MODE: MR_AUTO
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: Ensemble of 2OSS, 2OUO, 2GRC, 2OO1, 3DAI, 3D7C, 3DWY Resolution: 1.34→29.22 Å / Cor.coef. Fo:Fc: 0.974 / Cor.coef. Fo:Fc free: 0.964 / SU B: 2.271 / SU ML: 0.042 / SU R Cruickshank DPI: 0.0565 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.056 / ESU R Free: 0.057 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: 66.62 Å2 / Biso mean: 19.083 Å2 / Biso min: 9.39 Å2
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Refinement step | Cycle: final / Resolution: 1.34→29.22 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.34→1.375 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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