4V0I

Water Network Determines Selectivity for a Series of Pyrimidone Indoline Amide PI3KBeta Inhibitors over PI3K-Delta

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1		6.5	292	PEG8000 5-10%, ETHYLENE GLYCOL 10-20%, CARBOXYLIC ACIDS 100MM, IN MES-IMIDAZOLE 100MM BUFFER PH 6.5 AT 19C

Crystal Properties
Matthews coefficient	Solvent content
2.73	54.9

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 62	α = 90
b = 216.43	β = 113.29
c = 76.97	γ = 90

Symmetry
Space Group	P 1 21 1

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 315r	TOROIDAL MIRROR	2011-02-17	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	ESRF BEAMLINE ID14-4		ESRF	ID14-4

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	2.54	216.43	99.4	0.07	11.8	3.3		60528		2	60.4

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	2.54	2.68	99.5		0.46	2.1	3

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	PDB ENTRY 2WXF	2.54	44.7	60472	3070	98.84	0.266	0.234		RANDOM	56.83

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]
1.3836		-4.5431	-4.1531		2.7695

RMS Deviations
Key	Refinement Restraint Deviation
t_other_torsion	20.02
t_omega_torsion	1.8
t_angle_deg	0.95
t_bond_d	0.008
t_dihedral_angle_d
t_incorr_chiral_ct
t_pseud_angle
t_trig_c_planes
t_gen_planes
t_it

RMS Deviations
Key	Refinement Restraint Deviation
t_other_torsion	20.02
t_omega_torsion	1.8
t_angle_deg	0.95
t_bond_d	0.008
t_dihedral_angle_d
t_incorr_chiral_ct
t_pseud_angle
t_trig_c_planes
t_gen_planes
t_it
t_nbd
t_improper_torsion
t_chiral_improper_torsion
t_sum_occupancies
t_utility_distance
t_utility_angle
t_utility_torsion
t_ideal_dist_contact

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	12462
Nucleic Acid Atoms
Solvent Atoms	140
Heterogen Atoms	52

Software

Software
Software Name	Purpose
BUSTER	refinement
XDS	data reduction
SCALA	data scaling
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.