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Yorodumi- PDB-6ft3: Crystal Structure of the first bromodomain of human BRD4 in compl... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6ft3 | ||||||
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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 / chromatin / 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: 1.28 Å | ||||||
Authors | Filippakopoulos, P. / Picaud, S. / Pike, A.C.W. / Krojer, T. / Conway, S.J. / 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 | 6ft3.cif.gz | 77.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6ft3.ent.gz | 56.2 KB | Display | PDB format |
PDBx/mmJSON format | 6ft3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6ft3_validation.pdf.gz | 747.6 KB | Display | wwPDB validaton report |
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Full document | 6ft3_full_validation.pdf.gz | 747.5 KB | Display | |
Data in XML | 6ft3_validation.xml.gz | 9.2 KB | Display | |
Data in CIF | 6ft3_validation.cif.gz | 13 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ft/6ft3 ftp://data.pdbj.org/pub/pdb/validation_reports/ft/6ft3 | HTTPS FTP |
-Related structure data
Related structure data | 6fsyC 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 | ChemComp-EDO / |
#3: Chemical | ChemComp-E5T / |
#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: 2.18 Å3/Da / Density % sol: 43.46 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 6.5 / Details: 0.1 M K(citrate) 0.1 M cacodylate pH 6.5 |
-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: 1.279→29.47 Å / Num. obs: 34700 / % possible obs: 99.6 % / Redundancy: 5.9 % / Rmerge(I) obs: 0.083 / Rpim(I) all: 0.036 / Rrim(I) all: 0.091 / Rsym value: 0.083 / Net I/av σ(I): 4.9 / Net I/σ(I): 10.8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 1.28→29.47 Å / Cor.coef. Fo:Fc: 0.976 / Cor.coef. Fo:Fc free: 0.96 / SU B: 1.775 / SU ML: 0.034 / SU R Cruickshank DPI: 0.0471 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.047 / ESU R Free: 0.048 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: 60.16 Å2 / Biso mean: 15.086 Å2 / Biso min: 6.99 Å2
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Refinement step | Cycle: final / Resolution: 1.28→29.47 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.28→1.313 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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