5TD2

Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	8.5	293	29% PEG 400 0.2M MgCl2 0.1M Tris pH 8.5

Crystal Properties
Matthews coefficient	Solvent content
2.46	50.03

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 51.157	α = 90
b = 91.942	β = 99.51
c = 69.655	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	ADSC QUANTUM 315r		2010-05-20	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	2.68	50	92.8	0.103	9.5	2.9		16671

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	2.68	2.73	62.4		0.439		2.1

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	2.68	30	15822	805	92.42	0.2507	0.2481	0.2999	RANDOM	64.709

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]
7.47		-2.06	-2.68		-3.87

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	35.437
r_dihedral_angle_4_deg	16.989
r_dihedral_angle_3_deg	15.483
r_mcangle_it	6.904
r_dihedral_angle_1_deg	5.6
r_mcbond_other	4.361
r_mcbond_it	4.36
r_angle_refined_deg	1.174
r_angle_other_deg	0.972
r_chiral_restr	0.063

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	35.437
r_dihedral_angle_4_deg	16.989
r_dihedral_angle_3_deg	15.483
r_mcangle_it	6.904
r_dihedral_angle_1_deg	5.6
r_mcbond_other	4.361
r_mcbond_it	4.36
r_angle_refined_deg	1.174
r_angle_other_deg	0.972
r_chiral_restr	0.063
r_bond_refined_d	0.007
r_gen_planes_refined	0.004
r_bond_other_d	0.002
r_gen_planes_other	0.002

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	3892
Nucleic Acid Atoms
Solvent Atoms	24
Heterogen Atoms	35

Software

Software
Software Name	Purpose
SCALEPACK	data scaling
REFMAC	refinement
PDB_EXTRACT	data extraction
HKL-2000	data reduction
PHASER	phasing

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), 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 R01GM157729.