4AGW

Discovery of a small molecule type II inhibitor of wild-type and gatekeeper mutants of BCR-ABL, PDGFRalpha, Kit, and Src kinases

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP		298	PROTEIN CONCENTRATION 0.3 MM INHIBITOR CONCENTRATION 0.5 MM METHOD HANGING DROP VAPOR DIFFUSION AT 298 K PROTEIN BUFFER 5 % DMSO, 20 MM TRIS PH 8.0, 250 MM NACL, 5 % GLYCEROL, 1 MM DTT. MOTHER LIQUOR: 100 MM MES PH 6.5, 7.5 % PEG 3350, 10 % GLYCEROL, 1 MM DTT

Crystal Properties
Matthews coefficient	Solvent content
2.7	54.42

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 40.738	α = 79.57
b = 61.393	β = 89.1
c = 71.814	γ = 90.14

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	ADSC QUANTUM 315r		2009-04-24	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	ALS BEAMLINE 8.2.1		ALS	8.2.1

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	2.5	50	93.4	0.11	7.2			19430

Refinement

Statistics
Diffraction ID	Structure Solution 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	OTHER	NONE	2.6	42.267	0.1	19430	1547	92.23	0.2295	0.2258	0.2713

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]
-8.2769	-0.1409	-0.0518	-3.5687	7.2138	11.8456

RMS Deviations
Key	Refinement Restraint Deviation
f_dihedral_angle_d	18.715
f_angle_d	1.57
f_chiral_restr	0.132
f_plane_restr	0.011
f_bond_d	0.01

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	4151
Nucleic Acid Atoms
Solvent Atoms	152
Heterogen Atoms	116

Software

Software
Software Name	Purpose
PHENIX	refinement
HKL-2000	data reduction
SCALEPACK	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.