5TT7

Discovery of TAK-659, an Orally Available Investigational Inhibitor of Spleen Tyrosine Kinase (SYK)

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP	8.7	293	1.2M Potassium Na Tartrate, 0.1M Tris pH 8.7

Crystal Properties
Matthews coefficient	Solvent content
2.36	47.83

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 39.815	α = 90
b = 85.204	β = 90
c = 88.912	γ = 90

Symmetry
Space Group	P 21 21 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 315r		2009-10-22	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	ALS BEAMLINE 5.0.3	0.9764848	ALS	5.0.3

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	1.76	50	98.9	0.082	10.2	5.5		30241

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	1.77	1.8	97.2		0.675		4.3

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	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	1.77	30	28640	1504	98.53	0.2076	0.2062	0.2345	RANDOM	29.668

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]
-1.24			-1.53		2.78

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	36.694
r_dihedral_angle_4_deg	17.139
r_dihedral_angle_3_deg	12.249
r_dihedral_angle_1_deg	5.233
r_mcangle_it	1.294
r_angle_refined_deg	1.15
r_angle_other_deg	1.141
r_mcbond_other	0.733
r_mcbond_it	0.732
r_chiral_restr	0.065

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	36.694
r_dihedral_angle_4_deg	17.139
r_dihedral_angle_3_deg	12.249
r_dihedral_angle_1_deg	5.233
r_mcangle_it	1.294
r_angle_refined_deg	1.15
r_angle_other_deg	1.141
r_mcbond_other	0.733
r_mcbond_it	0.732
r_chiral_restr	0.065
r_bond_refined_d	0.007
r_gen_planes_refined	0.004
r_bond_other_d	0.002
r_gen_planes_other	0.001

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2238
Nucleic Acid Atoms
Solvent Atoms	145
Heterogen Atoms	26

Software

Software
Software Name	Purpose
HKL-2000	data scaling
REFMAC	refinement
PDB_EXTRACT	data extraction
HKL-2000	data reduction
MOLREP	phasing
DENZO	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.