4Z1Q

Crystal structure of the first bromodomain of human BRD4 bound to benzotriazolo-diazepine scaffold

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP		277	0.2 M sodium chloride, 0.1 M Bis-Tris pH 6.5, and 25% polyethylene glycol (PEG) 3350

Crystal Properties
Matthews coefficient	Solvent content
2.19	43.88

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 30.293	α = 83.07
b = 39.501	β = 75.35
c = 57.23	γ = 89.85

Symmetry
Space Group	P 1

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray	100	CCD	RAYONIX MX300HS		2015-02-23	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	APS BEAMLINE 22-ID	1.000	APS	22-ID

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (Observed)	Rrim I (All)	Rpim I (All)	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	1.399	50	84.9	0.071	0.1	0.071	10.9	1.8		42635

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	Rrim I (All)	Rpim I (All)	CC (Half)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	1.399	1.45	54.6		0.428	0.606	0.428	0.617		1.1	2749

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Starting model	Resolution (High)	Resolution (Low)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (Observed)	R-Work	R-Free	R-Free Selection Details	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	THROUGHOUT	Internal model	1.399	50	40551	2084	84.74	0.2053	0.2034	0.2423	RANDOM	16.187

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]
0.01	-0.18	0.05	-0.67	-0.22	0.54

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	37.981
r_dihedral_angle_4_deg	20.55
r_dihedral_angle_3_deg	15.914
r_dihedral_angle_1_deg	5.325
r_angle_refined_deg	2.064
r_mcangle_it	1.653
r_mcbond_it	1.054
r_mcbond_other	1.054
r_angle_other_deg	0.987
r_chiral_restr	0.125

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	37.981
r_dihedral_angle_4_deg	20.55
r_dihedral_angle_3_deg	15.914
r_dihedral_angle_1_deg	5.325
r_angle_refined_deg	2.064
r_mcangle_it	1.653
r_mcbond_it	1.054
r_mcbond_other	1.054
r_angle_other_deg	0.987
r_chiral_restr	0.125
r_bond_refined_d	0.022
r_gen_planes_refined	0.012
r_bond_other_d	0.003
r_gen_planes_other	0.001

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2091
Nucleic Acid Atoms
Solvent Atoms	209
Heterogen Atoms	60

Software

Software
Software Name	Purpose
HKL-2000	data collection
SCALEPACK	data scaling
REFMAC	refinement
PDB_EXTRACT	data extraction
HKL-2000	data reduction
PHASER	phasing

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.