4EZL

Potent and Selective Inhibitors of PI3K-delta: Obtaining Isoform Selectivity from the Affinity Pocket and Tryptophan Shelf

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	8.5	289	PEG 3350, 0.2M NH4SO4, 0.1M Tris-HCl 8.5, vapor diffusion, hanging drop, temperature 289K

Crystal Properties
Matthews coefficient	Solvent content
2.27	45.87

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 141.331	α = 90
b = 67.194	β = 96.1
c = 106.558	γ = 90

Symmetry
Space Group	C 1 2 1

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray		CCD	ADSC QUANTUM 210		2011-10-26		SINGLE

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	ALS BEAMLINE 5.0.1	1.0	ALS	5.0.1

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	2.935	50	99.5	0.086	10.1	3.6		20407			80

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	2.935	3.11	99.8		0.475		3.7

Refinement

Statistics
Diffraction ID	Structure Solution Method	Starting model	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	PDB ENTRY 1E8X	2.94	31.14	1.35	20402	1044	94.9	0.245	0.244	0.271	102.31

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]
4.827		0.6987	4.0965		4.6886

RMS Deviations
Key	Refinement Restraint Deviation
f_dihedral_angle_d	13.637
f_angle_d	1.531
f_chiral_restr	0.068
f_bond_d	0.008
f_plane_restr	0.007

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	6735
Nucleic Acid Atoms
Solvent Atoms	1
Heterogen Atoms	34

Software

Software
Software Name	Purpose
DENZO	data reduction
SCALEPACK	data scaling
PHASER	phasing
PHENIX	refinement
PDB_EXTRACT	data extraction

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.