5LN2

Discovery of a novel class of highly potent inhibitors of the p53-MDM2 interaction by structure-based design starting from a conformational argument

X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
Type	Source	Accession Code	Details
experimental model	PDB	4ZYF

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	5	298	2.5M (NH4)2SO4, 0.1M NaCitrate

Crystal Properties
Matthews coefficient	Solvent content
2.15	42.78

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 56.54	α = 90
b = 56.54	β = 90
c = 103.953	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	CCD	MARMOSAIC 225 mm CCD		2010-09-14	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	SLS BEAMLINE X06DA	1.0000	SLS	X06DA

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	1.58	20	99.8	0.045	48	22.2		14090			24.5

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	1.58	20	99.1		0.277	10.3	14.9

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	4ZYF	1.58	18.51	13384	704	99.81	0.2164	0.2148	0.2474	RANDOM	19.35

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
r_dihedral_angle_2_deg	45.493
r_dihedral_angle_3_deg	13.865
r_dihedral_angle_4_deg	11.633
r_dihedral_angle_1_deg	5.401
r_mcangle_it	1.429
r_angle_refined_deg	1.009
r_scbond_it	0.999
r_mcbond_it	0.807
r_chiral_restr	0.071
r_bond_refined_d	0.007

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	45.493
r_dihedral_angle_3_deg	13.865
r_dihedral_angle_4_deg	11.633
r_dihedral_angle_1_deg	5.401
r_mcangle_it	1.429
r_angle_refined_deg	1.009
r_scbond_it	0.999
r_mcbond_it	0.807
r_chiral_restr	0.071
r_bond_refined_d	0.007
r_gen_planes_refined	0.006

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	779
Nucleic Acid Atoms
Solvent Atoms	116
Heterogen Atoms	47

Software

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

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.