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Yorodumi- PDB-7r9c: Cocrystal of BRD4(D1) with N,N-dimethyl-2-[(3R)-3-(5-{2-[2-methyl... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7r9c | ||||||
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Title | Cocrystal of BRD4(D1) with N,N-dimethyl-2-[(3R)-3-(5-{2-[2-methyl-5-(propan-2-yl)phenoxy]pyrimidin-4-yl}-4-[4-(trifluoromethyl)phenyl]-1H-imidazol-1-yl)pyrrolidin-1-yl]ethan-1-amine | ||||||
Components | Bromodomain-containing protein 4 | ||||||
Keywords | GENE REGULATION/INHIBITOR / BRD4 / GENE REGULATION / GENE REGULATION-INHIBITOR complex | ||||||
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: 1.5 Å | ||||||
Authors | Cui, H. / Shi, K. / Aihara, H. / Pomerantz, W.C.K. | ||||||
Funding support | United States, 1items
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Citation | Journal: J.Med.Chem. / Year: 2022 Title: A Structure-based Design Approach for Generating High Affinity BRD4 D1-Selective Chemical Probes. Authors: Cui, H. / Divakaran, A. / Hoell, Z.J. / Ellingson, M.O. / Scholtz, C.R. / Zahid, H. / Johnson, J.A. / Griffith, E.C. / Gee, C.T. / Lee, A.L. / Khanal, S. / Shi, K. / Aihara, H. / Shah, V.H. ...Authors: Cui, H. / Divakaran, A. / Hoell, Z.J. / Ellingson, M.O. / Scholtz, C.R. / Zahid, H. / Johnson, J.A. / Griffith, E.C. / Gee, C.T. / Lee, A.L. / Khanal, S. / Shi, K. / Aihara, H. / Shah, V.H. / Lee, R.E. / Harki, D.A. / Pomerantz, W.C.K. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7r9c.cif.gz | 111.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7r9c.ent.gz | 82.7 KB | Display | PDB format |
PDBx/mmJSON format | 7r9c.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7r9c_validation.pdf.gz | 772.7 KB | Display | wwPDB validaton report |
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Full document | 7r9c_full_validation.pdf.gz | 776.3 KB | Display | |
Data in XML | 7r9c_validation.xml.gz | 8.8 KB | Display | |
Data in CIF | 7r9c_validation.cif.gz | 11.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r9/7r9c ftp://data.pdbj.org/pub/pdb/validation_reports/r9/7r9c | HTTPS FTP |
-Related structure data
Related structure data | 7rxrC 7rxsC 7rxtC 6wgxS 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 BL21(DE3) (bacteria) / Variant (production host): BL21(DE3) / References: UniProt: O60885 | ||||||||
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#2: Chemical | ChemComp-EDO / #3: Chemical | ChemComp-2IR / | #4: Chemical | ChemComp-CL / | #5: 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: 2.07 Å3/Da / Density % sol: 40.47 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, hanging drop / Details: 0.1 M bis-tris propane, 20 % PEG 3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.979 Å | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Dec 3, 2020 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.979 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 1.5→35.57 Å / Num. obs: 19998 / % possible obs: 97 % / Redundancy: 4.7 % / Biso Wilson estimate: 25 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.068 / Rpim(I) all: 0.034 / Rrim(I) all: 0.076 / Net I/σ(I): 16.6 / Num. measured all: 94421 / Scaling rejects: 811 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6WGX Resolution: 1.5→35.57 Å / SU ML: 0.15 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 27.52 / Stereochemistry target values: ML
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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 max: 88.1 Å2 / Biso mean: 38.4718 Å2 / Biso min: 18.4 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.5→35.57 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 7
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