5LAW

Novel Spiro[3H-indole-3,2 -pyrrolidin]-2(1H)-one Inhibitors of the MDM2-p53 Interaction: HDM2 (MDM2) IN COMPLEX WITH COMPOUND 14

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	4.5	277	RESERVOIR SOLUTION : NULL

Crystal Properties
Matthews coefficient	Solvent content
2.27	45.79

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 56.219	α = 90
b = 56.219	β = 90
c = 105.128	γ = 120

Symmetry
Space Group	P 61 2 2

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray	100	PIXEL	DECTRIS PILATUS 6M		2013-07-21	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	SLS BEAMLINE X06SA	1.00003	SLS	X06SA

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	1.64	48.68	96.3	0.067	10.62	2.7		12213

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	1.64	1.89	96.6		0.44		2.9

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	MOLECULAR REPLACEMENT	THROUGHOUT	1.64	48.68	11012	1200	96.27	0.1952	0.1929	0.2158	RANDOM	12.93

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]
0.48	0.24		0.48		-0.72

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	42.842
r_dihedral_angle_4_deg	21.63
r_dihedral_angle_3_deg	12.105
r_dihedral_angle_1_deg	5.203
r_angle_refined_deg	1.364
r_angle_other_deg	1.029
r_chiral_restr	0.078
r_bond_refined_d	0.01
r_gen_planes_refined	0.007
r_bond_other_d	0.002

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	42.842
r_dihedral_angle_4_deg	21.63
r_dihedral_angle_3_deg	12.105
r_dihedral_angle_1_deg	5.203
r_angle_refined_deg	1.364
r_angle_other_deg	1.029
r_chiral_restr	0.078
r_bond_refined_d	0.01
r_gen_planes_refined	0.007
r_bond_other_d	0.002
r_gen_planes_other	0.001

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	773
Nucleic Acid Atoms
Solvent Atoms	43
Heterogen Atoms	53

Software

Software
Software Name	Purpose
REFMAC	refinement
PDB_EXTRACT	data extraction
XDS	data reduction
XSCALE	data scaling
REFMAC	phasing

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 R01GM157729.