2P4I

Evolution of a highly Selective and Potent 2-(Pyridin-2-yl)-1,3,5-triazine Tie-2 Kinase Inhibitor

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION	7	298	14-18% PEG 3350, 0.2M tri-Potassium Citrate (pH 6.5-7.5) and 2% isopropanol., pH 7.0, VAPOR DIFFUSION, temperature 298K

Crystal Properties
Matthews coefficient	Solvent content
2.46	49.95

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 64.262	α = 90
b = 63.189	β = 90
c = 175.571	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	IMAGE PLATE	RIGAKU RAXIS IV	mirrors	2003-06-23	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	ROTATING ANODE	RIGAKU RU300	1.5418

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	20	94.18	0.07	14.8		24255	22844	-1	-1

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)
	2.5	2.59	76.3		0.315	2		1897

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Resolution (High)	Resolution (Low)	Number Reflections (All)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (All)	R-Factor (Observed)	R-Work	R-Free	R-Free Selection Details	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	THROUGHOUT	2.5	20	24255	22844	1224	94.18	0.24846	0.24846	0.24558	0.30315	RANDOM	48.907

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]
1.4			1.14		-2.54

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	38.016
r_dihedral_angle_3_deg	17.053
r_dihedral_angle_4_deg	16.465
r_dihedral_angle_1_deg	5.549
r_scangle_it	1.671
r_angle_refined_deg	1.222
r_scbond_it	1.059
r_mcangle_it	0.95
r_mcbond_it	0.543
r_nbtor_refined	0.305

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	38.016
r_dihedral_angle_3_deg	17.053
r_dihedral_angle_4_deg	16.465
r_dihedral_angle_1_deg	5.549
r_scangle_it	1.671
r_angle_refined_deg	1.222
r_scbond_it	1.059
r_mcangle_it	0.95
r_mcbond_it	0.543
r_nbtor_refined	0.305
r_symmetry_vdw_refined	0.229
r_nbd_refined	0.208
r_xyhbond_nbd_refined	0.177
r_symmetry_hbond_refined	0.095
r_chiral_restr	0.083
r_bond_refined_d	0.01
r_gen_planes_refined	0.004

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	3965
Nucleic Acid Atoms
Solvent Atoms	178
Heterogen Atoms	82

Software

Software
Software Name	Purpose
REFMAC	refinement
CrystalClear	data collection
DENZO	data reduction
SCALEPACK	data scaling
AMoRE	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.