5T8E

Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs). Part II: Optimization of 4-(pyrrolidin-1-yl)benzonitrile derivatives

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP	7.2	293	Protein Storage Buffer: 25mM HEPES pH 7.2, 150mM LiSO4, 10mM DTT, 10% Glycerol, 0.1% bOG, 100uM inhibitor Crystallization Buffer: ~1M ammonium phosphate dibasic

Crystal Properties
Matthews coefficient	Solvent content
2.18	43.55

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 53.804	α = 90
b = 66.195	β = 90
c = 70.932	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	80	CCD	ADSC QUANTUM 315r		2006-07-22	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	ALS BEAMLINE 5.0.2	1.0	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	2.7	35.98	95.6	0.077	16.9	6.7		6954

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)
1	2.7	2.8	81.6		0.234		5.7

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		THROUGHOUT	2.71	35.98	6592	327	95.22	0.1757	0.1726	0.2381	RANDOM	67.085

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]
-1.6			0.5		1.1

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	32.1
r_dihedral_angle_3_deg	13.805
r_dihedral_angle_4_deg	12.852
r_dihedral_angle_1_deg	4.971
r_mcangle_it	3.192
r_mcbond_it	1.964
r_mcbond_other	1.96
r_angle_refined_deg	1.003
r_angle_other_deg	0.696
r_chiral_restr	0.052

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	32.1
r_dihedral_angle_3_deg	13.805
r_dihedral_angle_4_deg	12.852
r_dihedral_angle_1_deg	4.971
r_mcangle_it	3.192
r_mcbond_it	1.964
r_mcbond_other	1.96
r_angle_refined_deg	1.003
r_angle_other_deg	0.696
r_chiral_restr	0.052
r_bond_refined_d	0.007
r_gen_planes_refined	0.003
r_bond_other_d	0.001
r_gen_planes_other	0.001

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2033
Nucleic Acid Atoms
Solvent Atoms	38
Heterogen Atoms	29

Software

Software
Software Name	Purpose
REFMAC	refinement
SCALEPACK	data scaling
PDB_EXTRACT	data extraction
HKL-2000	data reduction
MOLREP	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.