3PTG

Design and Synthesis of a Novel, Orally Efficacious Tri-substituted Thiophene Based JNK Inhibitor

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP	5.5	277	20% PEG3000, 0.1 M sodium citrate, 15% glycerol, pH 5.5, VAPOR DIFFUSION, SITTING DROP, temperature 277K

Crystal Properties
Matthews coefficient	Solvent content
2.32	47

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 59.772	α = 90
b = 80.434	β = 90
c = 83.45	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 210r		2007-02-28	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	APS BEAMLINE 19-BM	0.9788	APS	19-BM

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (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	2.43	57.93	88.23			13169	13169	1	1

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
	2.43	2.493	91.2

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 (Observed)	R-Work	R-Free	R-Free Selection Details	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	THROUGHOUT	2.43	34.21	13169	13169	701	88.23	0.2475	0.24384	0.31597	RANDOM	50.532

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]
1.12			-0.61		-0.51

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	34.717
r_dihedral_angle_3_deg	20.881
r_dihedral_angle_4_deg	17.51
r_dihedral_angle_1_deg	8.045
r_scangle_it	2.95
r_angle_refined_deg	2.025
r_scbond_it	1.943
r_mcangle_it	1.65
r_mcbond_it	0.96
r_nbtor_refined	0.31

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	34.717
r_dihedral_angle_3_deg	20.881
r_dihedral_angle_4_deg	17.51
r_dihedral_angle_1_deg	8.045
r_scangle_it	2.95
r_angle_refined_deg	2.025
r_scbond_it	1.943
r_mcangle_it	1.65
r_mcbond_it	0.96
r_nbtor_refined	0.31
r_nbd_refined	0.253
r_symmetry_hbond_refined	0.25
r_symmetry_vdw_refined	0.243
r_xyhbond_nbd_refined	0.193
r_chiral_restr	0.126
r_bond_refined_d	0.017
r_gen_planes_refined	0.006

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2841
Nucleic Acid Atoms
Solvent Atoms	28
Heterogen Atoms	26

Software

Software
Software Name	Purpose
HKL-2000	data collection
AMoRE	phasing
REFMAC	refinement
HKL-2000	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.