6YQN
Crystal structure of the first bromodomain of human BRD4 in complex with the dual inhibitor TW9
X-RAY DIFFRACTION
Starting Model(s)
Initial Refinement Model(s) | |||
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Type | Source | Accession Code | Details |
experimental model | PDB | 3MXF |
Crystallization
Crystalization Experiments | ||||
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ID | Method | pH | Temperature | Details |
1 | VAPOR DIFFUSION, SITTING DROP | 277 | Protein solution: 10 mg/ml in 10 mM HEPES, pH 7.5, 150 mM NaCl, 0.5 mM TCEP, and 5% glycerol. 50 mM stock solution of TW12 in DMSO added to give a final inhibitor concentration 1.5 mM. Reservoir buffer: 24% PEG 3350, 0.1 M sodium formate, 15% ethylene glycol and 0.1 M bis-Tris-propane pH 7.3. Ratio protein/reservoir solution = 2:1 |
Crystal Properties | |
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Matthews coefficient | Solvent content |
2.14 | 42.53 |
Crystal Data
Unit Cell | |
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Length ( Å ) | Angle ( ˚ ) |
a = 37.254 | α = 90 |
b = 44.338 | β = 90 |
c = 78.256 | γ = 90 |
Symmetry | |
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Space Group | P 21 21 21 |
Diffraction
Diffraction Experiment | ||||||||||||||
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ID # | Crystal ID | Scattering Type | Data Collection Temperature | Detector | Detector Type | Details | Collection Date | Monochromator | Protocol | |||||
1 | 1 | x-ray | 100 | PIXEL | DECTRIS PILATUS3 6M | 2017-11-30 | M | SINGLE WAVELENGTH |
Radiation Source | |||||
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ID # | Source | Type | Wavelength List | Synchrotron Site | Beamline |
1 | SYNCHROTRON | ESRF BEAMLINE ID30B | 0.70848 | ESRF | ID30B |
Data Collection
Overall | |||||||||||||||||||
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ID # | Resolution (High) | Resolution (Low) | Percent Possible (Observed) | R Merge I (Observed) | CC (Half) | Net I Over Average Sigma (I) | Redundancy | Number Reflections (All) | Number Reflections (Observed) | Observed Criterion Sigma (F) | Observed Criterion Sigma (I) | B (Isotropic) From Wilson Plot | |||||||
1 | 1.05 | 78.3 | 100 | 0.084 | 0.998 | 14.3 | 11.6 | 61370 | 9.65991112921 |
Highest Resolution Shell | |||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ID # | Resolution (High) | Resolution (Low) | Percent Possible (All) | Percent Possible (Observed) | R Merge I (Observed) | CC (Half) | Mean I Over Sigma (Observed) | Redundancy | Number Unique Reflections (All) | ||||||||||
1 | 1.05 | 1.07 | 0.69 | 0.896 | 2.8 |
Refinement
Statistics | |||||||||||||||||||
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Diffraction ID | Structure Solution Method | Cross Validation method | Starting model | Resolution (High) | Resolution (Low) | Cut-off Sigma (F) | Number Reflections (Observed) | Number Reflections (R-Free) | Percent Reflections (Observed) | R-Factor (Observed) | R-Work | R-Free | Mean Isotropic B | ||||||
X-RAY DIFFRACTION | FOURIER SYNTHESIS | FREE R-VALUE | 3MXF | 1.05 | 39.15 | 1.33737477503 | 61260 | 3095 | 99.9396381552 | 0.164805061865 | 0.164199975376 | 0.176224999275 | 14.181153913 |
Temperature Factor Modeling | ||||||
---|---|---|---|---|---|---|
Anisotropic B[1][1] | Anisotropic B[1][2] | Anisotropic B[1][3] | Anisotropic B[2][2] | Anisotropic B[2][3] | Anisotropic B[3][3] | |
RMS Deviations | |
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Key | Refinement Restraint Deviation |
f_dihedral_angle_d | 10.8622616378 |
f_angle_d | 0.82195939178 |
f_chiral_restr | 0.0741496552007 |
f_plane_restr | 0.00545915163667 |
f_bond_d | 0.00497251855873 |
Non-Hydrogen Atoms Used in Refinement | |
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Non-Hydrogen Atoms | Number |
Protein Atoms | 1019 |
Nucleic Acid Atoms | |
Solvent Atoms | 147 |
Heterogen Atoms | 35 |
Software
Software | |
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Software Name | Purpose |
PHENIX | refinement |
XDS | data reduction |
Aimless | data scaling |
PHENIX | phasing |