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Yorodumi- PDB-4men: Crystal Structure of the first bromodomain of human BRD4 in compl... -
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-Basic information
Entry | Database: PDB / ID: 4men | ||||||
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Title | Crystal Structure of the first bromodomain of human BRD4 in complex with a 5-methyl-triazolopyrimidine ligand | ||||||
Components | Bromodomain-containing protein 4 | ||||||
Keywords | TRANSCRIPTION/TRANSCRIPTION inhibitor / BRD4 / CAP / HUNK1 / MCAP / Mitotic chromosome associated protein / BRD / Small molecule inhibitor / Structural Genomics COnsortium / SGC / TRANSCRIPTION-TRANSCRIPTION 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 / 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 / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.81 Å | ||||||
Authors | Filippakopoulos, P. / Picaud, S. / Felletar, I. / Martin, S. / Fedorov, O. / Vidler, L.R. / Brown, N. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. ...Filippakopoulos, P. / Picaud, S. / Felletar, I. / Martin, S. / Fedorov, O. / Vidler, L.R. / Brown, N. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Weigelt, J. / Bountra, C. / Hoelder, S. / Knapp, S. / Structural Genomics Consortium (SGC) | ||||||
Citation | Journal: J.Med.Chem. / Year: 2013 Title: Discovery of Novel Small-Molecule Inhibitors of BRD4 Using Structure-Based Virtual Screening. Authors: Vidler, L.R. / Filippakopoulos, P. / Fedorov, O. / Picaud, S. / Martin, S. / Tomsett, M. / Woodward, H. / Brown, N. / Knapp, S. / Hoelder, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4men.cif.gz | 70.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4men.ent.gz | 50.3 KB | Display | PDB format |
PDBx/mmJSON format | 4men.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4men_validation.pdf.gz | 743.9 KB | Display | wwPDB validaton report |
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Full document | 4men_full_validation.pdf.gz | 744 KB | Display | |
Data in XML | 4men_validation.xml.gz | 9.5 KB | Display | |
Data in CIF | 4men_validation.cif.gz | 13.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/me/4men ftp://data.pdbj.org/pub/pdb/validation_reports/me/4men | HTTPS FTP |
-Related structure data
Related structure data | 4meoC 4mepC 4meqC 2ossS C: citing same article (ref.) S: Starting model for refinement |
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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 / Fragment: unp residues 44-168 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)-R3 / References: UniProt: O60885 |
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#2: Chemical | ChemComp-EDO / |
#3: Chemical | ChemComp-25K / |
#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: 2.14 Å3/Da / Density % sol: 42.62 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: 0.20M Na(malonate), 0.1M BTProp, 20.0% PEG 3350 10.0% EtGly, pH 8.5, VAPOR DIFFUSION, SITTING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.52 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Mar 16, 2012 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.52 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Redundancy: 4.3 % / Av σ(I) over netI: 2.8 / Number: 53429 / Rsym value: 0.144 / D res high: 1.805 Å / D res low: 28.611 Å / Num. obs: 12486 / % possible obs: 99.9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Diffraction reflection shell |
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Reflection | Resolution: 1.8→28.6 Å / Num. all: 12498 / Num. obs: 12486 / % possible obs: 99.9 % / Redundancy: 4.3 % / Biso Wilson estimate: 17.9 Å2 / Rmerge(I) obs: 0.144 / Rsym value: 0.144 / Net I/σ(I): 7.7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: PDB ENTRY 2OSS Resolution: 1.81→28.6 Å / Cor.coef. Fo:Fc: 0.958 / Cor.coef. Fo:Fc free: 0.919 / WRfactor Rfree: 0.2032 / WRfactor Rwork: 0.1534 / Occupancy max: 1 / Occupancy min: 0.5 / FOM work R set: 0.8884 / SU B: 4.612 / SU ML: 0.079 / SU R Cruickshank DPI: 0.1305 / SU Rfree: 0.1321 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.13 / ESU R Free: 0.132 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES: WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 95.11 Å2 / Biso mean: 16.6825 Å2 / Biso min: 6.15 Å2
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Refinement step | Cycle: LAST / Resolution: 1.81→28.6 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.805→1.852 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Origin x: 30.7516 Å / Origin y: 25.6944 Å / Origin z: 8.5833 Å
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