6M95

Structure-based Design, Synthesis, and Biological Evaluation of Imidazo[4,5-b]pyridine-2-one based p38 MAP Kinase Inhibitors by scaffold hopping: compound 1

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP	7.4	277.15	16.% PEG 3350, 0.06M MES, 0.04M MES_Na

Crystal Properties
Matthews coefficient	Solvent content
2.01	38.66

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 68.523	α = 90
b = 70.124	β = 90
c = 74.599	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 4		2007-09-01	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)	Rpim I (All)	CC (Half)	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	1.8	49.01	98.75	0.06831	0.03589	0.998	15.58	4.5		33573			19.14

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	Rpim I (All)	CC (Half)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	1.8	1.864	96.03		0.4724	0.2669	0.803	2.61	3.8

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	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	MOLECULAR REPLACEMENT	FREE R-VALUE	1.8	49.01	1.34	33571	1705	98.74	0.1743	0.1724	0.2084	22.72

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]

RMS Deviations
Key	Refinement Restraint Deviation
f_dihedral_angle_d	9.2293
f_angle_d	1.4646
f_chiral_restr	0.0962
f_bond_d	0.0154
f_plane_restr	0.0091

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2683
Nucleic Acid Atoms
Solvent Atoms	310
Heterogen Atoms	25

Software

Software
Software Name	Purpose
PHENIX	refinement
HKL-2000	data reduction
HKL-2000	data scaling
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 R01GM133198.