5TA4

Discovery of a Potent Cyclophilin Inhibitor (Compound 8) based on Structural Simplification of Sanglifehrin A

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION	8.5	293	0.1 M Tris-HCl, pH 8.5 0.2 M potassium chloride 2.0 M ammonium sulfate

Crystal Properties
Matthews coefficient	Solvent content
2.06	40.22

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 47.797	α = 90
b = 47.797	β = 90
c = 64.504	γ = 90

Symmetry
Space Group	P 43

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray	100	IMAGE PLATE	RIGAKU RAXIS IV		2011-03-07	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	ROTATING ANODE	RIGAKU MICROMAX-007 HF	1.54

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (Observed)	Rrim 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	1.5	19.2	99.9	0.043	0.043	20.7	4.49		23259			14.95

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	1.5	1.55	99.3		0.445	2.1	4.13

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		FREE R-VALUE	1.5	19.2	0.08	23203	1989	99.63	0.1785	0.1759	0.2062	15.416

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	11.715
f_angle_d	1.121
f_chiral_restr	0.048
f_bond_d	0.007
f_plane_restr	0.004

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	1258
Nucleic Acid Atoms
Solvent Atoms	168
Heterogen Atoms	45

Software

Software
Software Name	Purpose
d*TREK	data scaling
PHENIX	refinement
PDB_EXTRACT	data extraction

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.