6ANL

Structure-based Design, Synthesis, and Biological Evaluation of Imidazo[1,2-b]pyridazine-based p38 MAP Kinase Inhibitors

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP	7.4	293	15.% PEG 8000, 0.08M NP_HEPES, 0.02M NP_HEPES_Na

Crystal Properties
Matthews coefficient	Solvent content
2.17	43.35

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 69.954	α = 90
b = 69.703	β = 90
c = 74.294	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		2007-05-11	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	ALS BEAMLINE 5.0.3	1.0	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	50	99.8	0.064	14	4.3		25087

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	2.05	98.5		0.257		4

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		THROUGHOUT	2	50	23762	1278	99.67	0.2087	0.2058	0.2634	RANDOM	37.713

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]
0.65			0.77		-1.42

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	34.936
r_dihedral_angle_4_deg	18.791
r_dihedral_angle_3_deg	13.708
r_dihedral_angle_1_deg	5.706
r_angle_refined_deg	1.356
r_chiral_restr	0.091
r_bond_refined_d	0.009
r_gen_planes_refined	0.005

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2722
Nucleic Acid Atoms
Solvent Atoms	230
Heterogen Atoms	29

Software

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