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Yorodumi- PDB-7rmd: Crystal structure of the first bromodomain of human BRD4 in compl... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7rmd | ||||||
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Title | Crystal structure of the first bromodomain of human BRD4 in complex with SJ001011461-1 | ||||||
Components | Bromodomain-containing protein 4 | ||||||
Keywords | CELL CYCLE / bromodomain-containing protein 4 isoform long / BRD4 / bromodomain containing protein 4 / mitotic chromosome associated protein | ||||||
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: 1.18 Å | ||||||
Authors | Stachowski, T.R. / Fischer, M. | ||||||
Citation | Journal: Eur.J.Med.Chem. / Year: 2023 Title: From PROTAC to inhibitor: Structure-guided discovery of potent and orally bioavailable BET inhibitors. Authors: Koravovic, M. / Mayasundari, A. / Tasic, G. / Keramatnia, F. / Stachowski, T.R. / Cui, H. / Chai, S.C. / Jonchere, B. / Yang, L. / Li, Y. / Fu, X. / Hiltenbrand, R. / Paul, L. / Mishra, V. / ...Authors: Koravovic, M. / Mayasundari, A. / Tasic, G. / Keramatnia, F. / Stachowski, T.R. / Cui, H. / Chai, S.C. / Jonchere, B. / Yang, L. / Li, Y. / Fu, X. / Hiltenbrand, R. / Paul, L. / Mishra, V. / Klco, J.M. / Roussel, M.F. / Pomerantz, W.C. / Fischer, M. / Rankovic, Z. / Savic, V. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7rmd.cif.gz | 119.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7rmd.ent.gz | 84 KB | Display | PDB format |
PDBx/mmJSON format | 7rmd.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7rmd_validation.pdf.gz | 773.3 KB | Display | wwPDB validaton report |
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Full document | 7rmd_full_validation.pdf.gz | 774.4 KB | Display | |
Data in XML | 7rmd_validation.xml.gz | 9.9 KB | Display | |
Data in CIF | 7rmd_validation.cif.gz | 14.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rm/7rmd ftp://data.pdbj.org/pub/pdb/validation_reports/rm/7rmd | HTTPS FTP |
-Related structure data
Related structure data | 7rn2C 3mxfS S: Starting model for refinement 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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Unit cell |
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-Components
#1: Protein | Mass: 15099.380 Da / Num. of mol.: 1 / Fragment: UNP residues 44-168 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / 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-5Z0 / |
#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: 2.12 Å3/Da / Density % sol: 42.07 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 0.1 M Bis-Tris, pH 6.8, 20% PEG3350, 15% ethylene glycol |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 24, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.18→39.12 Å / Num. obs: 42281 / % possible obs: 98.15 % / Redundancy: 10.2 % / Biso Wilson estimate: 12.26 Å2 / CC1/2: 0.999 / Net I/σ(I): 22.09 |
Reflection shell | Resolution: 1.18→1.222 Å / Redundancy: 6.8 % / Rmerge(I) obs: 0.3614 / Num. unique obs: 3600 / CC1/2: 0.948 / % possible all: 85.3 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 3MXF Resolution: 1.18→39.12 Å / SU ML: 0.0911 / Cross valid method: FREE R-VALUE / σ(F): 1.39 / Phase error: 16.477 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: 16.9 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.18→39.12 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 29.9402094785 Å / Origin y: 25.4535697968 Å / Origin z: 9.06668096281 Å
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Refinement TLS group | Selection details: all |