5LWP

Discovery of phenoxyindazoles and phenylthioindazoles as RORg inverse agonists

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP		278	0.1M Hepes pH8.5, 0.1M MgCl2, 7% PEG6000

Crystal Properties
Matthews coefficient	Solvent content
3.49	64.75

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 173.81	α = 90
b = 173.81	β = 90
c = 68.4	γ = 120

Symmetry
Space Group	H 3 2

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray	278	PIXEL	DECTRIS PILATUS 6M	Kirkpatrick-Baez pair of bi-morph mirrors plus channel cut cryogenically cooled monochromator crystal	2014-09-16	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	SOLEIL BEAMLINE PROXIMA 1	0.97857	SOLEIL	PROXIMA 1

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (Observed)	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	29.313	99.7	0.057	0.999	21.98	7.07		15503		-3	55.298

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	CC (Half)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	2.4	2.54	99.1		0.509	0.923	3.98	7.1

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Starting model	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	3B0W	2.4	29.31	14726	776	99.75	0.2028	0.2001	0.2533	RANDOM	52.239

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]
-1.16	-0.58		-1.16		3.78

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	35.146
r_dihedral_angle_4_deg	19.915
r_dihedral_angle_3_deg	18.366
r_scbond_it	6.716
r_mcangle_it	6.528
r_dihedral_angle_1_deg	6.168
r_mcbond_it	4.736
r_angle_refined_deg	1.992
r_chiral_restr	0.139
r_bond_refined_d	0.018

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	35.146
r_dihedral_angle_4_deg	19.915
r_dihedral_angle_3_deg	18.366
r_scbond_it	6.716
r_mcangle_it	6.528
r_dihedral_angle_1_deg	6.168
r_mcbond_it	4.736
r_angle_refined_deg	1.992
r_chiral_restr	0.139
r_bond_refined_d	0.018
r_gen_planes_refined	0.01

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	1984
Nucleic Acid Atoms
Solvent Atoms	44
Heterogen Atoms	35

Software

Software
Software Name	Purpose
XSCALE	data scaling
PHASER	phasing
REFMAC	refinement
PDB_EXTRACT	data extraction
XDS	data reduction

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.