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Yorodumi- PDB-8p9i: Crystal structure of the first bromodomain of human BRD4 in compl... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8p9i | ||||||
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Title | Crystal structure of the first bromodomain of human BRD4 in complex with the dual BET/HDAC inhibitor NB462 | ||||||
Components | Bromodomain-containing protein 4 | ||||||
Keywords | GENE REGULATION / bromodomain / epigenetic drugs / inhibitor / cancer therapy | ||||||
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 / Resolution: 1.23 Å | ||||||
Authors | Balourdas, D.I. / Bauer, N. / Knapp, S. / Joerger, A.C. / Structural Genomics Consortium (SGC) | ||||||
Funding support | Germany, 1items
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Citation | Journal: Acs Chem.Biol. / Year: 2024 Title: Development of Potent Dual BET/HDAC Inhibitors via Pharmacophore Merging and Structure-Guided Optimization. Authors: Bauer, N. / Balourdas, D.I. / Schneider, J.R. / Zhang, X. / Berger, L.M. / Berger, B.T. / Schwalm, M.P. / Klopp, N.A. / Siveke, J.T. / Knapp, S. / Joerger, A.C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8p9i.cif.gz | 152.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8p9i.ent.gz | 100.2 KB | Display | PDB format |
PDBx/mmJSON format | 8p9i.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/p9/8p9i ftp://data.pdbj.org/pub/pdb/validation_reports/p9/8p9i | HTTPS FTP |
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-Related structure data
Related structure data | 8p9fC 8p9gC 8p9hC 8p9jC 8p9kC 8p9lC C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 15099.380 Da / Num. of mol.: 2 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 #2: Chemical | #3: Chemical | ChemComp-EDO / #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.02 Å3/Da / Density % sol: 39.29 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop Details: Protein solution: 10 mg/mL in 25 mM HEPES pH 7.5, 150 mM NaCl, 0.5 mM TCEP, 5% glycerol, 1 mM inhibitor NB462. Crystallization buffer: 24% PEG 3350, 0.15 M Na formate, 15% ethylene glycol, 0. ...Details: Protein solution: 10 mg/mL in 25 mM HEPES pH 7.5, 150 mM NaCl, 0.5 mM TCEP, 5% glycerol, 1 mM inhibitor NB462. Crystallization buffer: 24% PEG 3350, 0.15 M Na formate, 15% ethylene glycol, 0.1 M bis-tris propane pH 7.6. Vol. ratio 1:2 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Oct 15, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.23→44.7 Å / Num. obs: 68247 / % possible obs: 97.6 % / Redundancy: 4.9 % / Biso Wilson estimate: 15.12 Å2 / CC1/2: 0.991 / Rmerge(I) obs: 0.072 / Net I/σ(I): 8.8 |
Reflection shell | Resolution: 1.23→1.25 Å / Redundancy: 4.8 % / Rmerge(I) obs: 0.781 / Mean I/σ(I) obs: 2.3 / Num. unique obs: 3276 / CC1/2: 0.835 / % possible all: 95.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.23→44.68 Å / SU ML: 0.1647 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 21.127 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 20.08 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.23→44.68 Å
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Refine LS restraints |
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LS refinement shell |
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