3EY4

Further studies with the 2-amino-1,3-thiazol-4(5H)-one class of 11-hydroxysteroid dehydrogenase type 1 (11-HSD1) inhibitors: Reducing pregnane X receptor (PXR) activity and exploring activity in a monkey pharmacodynamic model

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	5.6	298	PEG 3350 25%, Na Citrate 0.1M, ammonium acetate 0.2M, pH 5.6, VAPOR DIFFUSION, HANGING DROP, temperature 298K

Crystal Properties
Matthews coefficient	Solvent content
2.16	43.13

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 49.043	α = 90
b = 138.482	β = 90
c = 155.336	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 315		2005-09-21	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)	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	2.9	50	97.6	0.113	12.014	4.3		24635

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
	2.9	3	83.2		0.614		2.6	2041

Refinement

Statistics
Diffraction ID	Structure Solution Method	Resolution (High)	Resolution (Low)	Number Reflections (All)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Work	R-Free	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	3	50	20693	20693	1643	94	0.219	0.319	43.133

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]
-6.462			0.939		5.523

RMS Deviations
Key	Refinement Restraint Deviation
c_scangle_it	2.698
c_mcangle_it	2.239
c_angle_deg	1.853
c_scbond_it	1.709
c_mcbond_it	1.284
c_bond_d	0.01

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	7895
Nucleic Acid Atoms
Solvent Atoms
Heterogen Atoms	276

Software

Software
Software Name	Purpose
CNX	refinement
SCALEPACK	data scaling
MOLREP	phasing
REFMAC	refinement
PDB_EXTRACT	data extraction
HKL-2000	data collection
DENZO	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.