4QVX

Discovery of a Potent and Selective BCL-XL Inhibitor That Demonstrates Thrombocytopenia and Inhibits Tumor Growth in Vivo

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP	8	290	10.73 uM compound in DMSO + 2.14 uM protein in 25 mM Tris, 0.1 M sodium chloride, 10% v/v glycerol, 1 mM DTT, pH 8.0 incubated overnight at 277K then concentrated to 12 mg/mL, 1:1 protein solution:reservoir solution (3 M sodium chloride, 0.1 M citric acid, pH 3.5) used in drop, VAPOR DIFFUSION, SITTING DROP, temperature 290K

Crystal Properties
Matthews coefficient	Solvent content
1.86	33.94

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 73.107	α = 90
b = 90.955	β = 90
c = 83.736	γ = 90

Symmetry
Space Group	C 2 2 21

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	ADSC QUANTUM 210		2010-12-16	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	APS BEAMLINE 17-ID	1.0	APS	17-ID

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	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	2.1	56.98	99.76			16611	16571	1	1	31.257

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	2.1	2.23	99.76

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Resolution (High)	Resolution (Low)	Cut-off Sigma (F)	Number Reflections (All)	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	2.1	56.98	1	16611	16571	837	99.76	0.1942	0.1911	0.257	RANDOM	33.38

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]
4.75142448			-1.53655263		-3.21487185

RMS Deviations
Key	Refinement Restraint Deviation
o_dihedral_angle_d	20.107
o_angle_deg	0.837
o_bond_d	0.005

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2186
Nucleic Acid Atoms
Solvent Atoms	153
Heterogen Atoms	94

Software

Software
Software Name	Purpose
ADSC	data collection
MOLREP	phasing
BUSTER-TNT	refinement
PROCESS	data reduction
PROCESS	data scaling

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.