3IK3

AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	8.5	277	0.1 M Tris-HCl (pH 8.5), 30% w/v polyethylene glycol 4000, and 0.2 M sodium acetate, VAPOR DIFFUSION, HANGING DROP, temperature 277K

Crystal Properties
Matthews coefficient	Solvent content
2.61	52.85

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 43.907	α = 90
b = 131.453	β = 92.87
c = 60.2	γ = 90

Symmetry
Space Group	P 1 21 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			2006-08-25	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	APS BEAMLINE 19-BM	0.979	APS	19-BM

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (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	1.9	50		0.081	16.1	4	53537	48583

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
	1.9	1.97	81.8		0.289	3.8	3.7	4324

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Starting model	Resolution (High)	Resolution (Low)	Number Reflections (All)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Work	R-Free	R-Free Selection Details	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	THROUGHOUT	PDB ENTRY 1IEP	1.9	50	52977	48583	2443	90.7	0.216	0.258	Random	19.278

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]
0.081		-0.053	-0.057		-0.024

RMS Deviations
Key	Refinement Restraint Deviation
c_scangle_it	3.05
c_scbond_it	2.222
c_mcangle_it	2.059
c_mcbond_it	1.449

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	4600
Nucleic Acid Atoms
Solvent Atoms	459
Heterogen Atoms	78

Software

Software
Software Name	Purpose
CNS	refinement
PDB_EXTRACT	data extraction
HKL-2000	data collection
HKL-2000	data reduction
HKL-2000	data scaling
CNS	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.