8IXS

Methyl and Fluorine Effects in Novel Orally Bioavailable Keap1/Nrf2 PPI Inhibitor for Treatment of Chronic Kidney Disease

X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
Type	Source	Accession Code	Details
experimental model	PDB	1U6D

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION	7.5	278	6-10mg/mL and crystallized with the solution with 0.1M Na acetate (pH5.0) and 1.5M di-ammonium sulfate or the solution with 0.1M Na acetate (pH5.0), 1.5M di-ammonium, and 0.1-0.15M NaCl

Crystal Properties
Matthews coefficient	Solvent content
2.46	50.03

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 103.589	α = 90
b = 103.589	β = 90
c = 55.19	γ = 120

Symmetry
Space Group	P 61

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	MARMOSAIC 225 mm CCD		2014-07-15	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	SPRING-8 BEAMLINE BL41XU	1.0	SPring-8	BL41XU

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (Observed)	Rrim I (All)	Rpim I (All)	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	1.48	89.71	99.5	0.092	0.093	0.017	3.9	29.2		56260

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	1.48	1.52	93.7		0.913	0.935	0.193	0.903	3.9	19.8

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	1.48	89.71	1.34	56220	2840	99.51	0.1654	0.1641	0.1905	21.83

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	10.5895
f_angle_d	0.5918
f_chiral_restr	0.0757
f_plane_restr	0.0049
f_bond_d	0.0022

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2251
Nucleic Acid Atoms
Solvent Atoms	426
Heterogen Atoms	58

Software

Software
Software Name	Purpose
PHENIX	refinement
XDS	data reduction
Aimless	data scaling
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.