6N3O

Identification of novel, potent and selective GCN2 inhibitors as first-in-class anti-tumor agents

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP		293	100 mM Na Citrate pH 5.6, 8% PEG 6K, 0.7 M LiCl, 1% Ethylene Glycol

Crystal Properties
Matthews coefficient	Solvent content
2.65	53.64

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 82.899	α = 90
b = 82.899	β = 90
c = 193.702	γ = 120

Symmetry
Space Group	P 61 2 2

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray	100	PIXEL	DECTRIS PILATUS3 6M		2016-04-08	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	ALS BEAMLINE 5.0.2	1	ALS	5.0.2

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (Observed)	Rrim I (All)	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	2.4	48.43	100	0.099	0.102	0.023	1	23.1	18.6		16229

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	Rrim I (All)	Rpim I (All)	CC (Half)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	2.4	2.49	100		3.621	3.716	0.831	0.46		19.6

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	2.4	25	15338	796	99.78	0.202	0.1992	0.2544	RANDOM	84.3

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	0.32		0.65		-2.1

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	32.084
r_dihedral_angle_4_deg	21.368
r_dihedral_angle_3_deg	15.013
r_dihedral_angle_1_deg	6.589
r_angle_refined_deg	1.436
r_angle_other_deg	1.144
r_chiral_restr	0.058
r_bond_refined_d	0.006
r_gen_planes_refined	0.005
r_bond_other_d	0.001

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	32.084
r_dihedral_angle_4_deg	21.368
r_dihedral_angle_3_deg	15.013
r_dihedral_angle_1_deg	6.589
r_angle_refined_deg	1.436
r_angle_other_deg	1.144
r_chiral_restr	0.058
r_bond_refined_d	0.006
r_gen_planes_refined	0.005
r_bond_other_d	0.001
r_gen_planes_other	0.001

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2069
Nucleic Acid Atoms
Solvent Atoms	17
Heterogen Atoms	30

Software

Software
Software Name	Purpose
REFMAC	refinement
HKL-2000	data scaling
PDB_EXTRACT	data extraction
XDS	data reduction
PHASER	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.