4ZYI

Discovery of NVP-CGM097 - a highly potent and selective MDM2 inhibitor undergoing phase 1 clinical trials in p53wt tumors: Hdm2 (MDM2) complexed with cpd2

X-RAY DIFFRACTION

Starting Model(s)

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

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	4.7	298	reservoir: 2.2M AmmoniumSulfate, 0.1M cictric acid, pH4.7. protein: 7mg/ml Hdm2 in 50mM TRIS pH8.0, 200mM NaCl, 1mM TCEP, 10% glycerol. drop: 1ul reservoir + 1ul protein

Crystal Properties
Matthews coefficient	Solvent content
2.16	43

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 55.748	α = 90
b = 55.748	β = 90
c = 107.324	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	MARRESEARCH		2009-02-13	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	SLS BEAMLINE X10SA	1.00001	SLS	X10SA

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	1.67	20	99.9	0.047	94.14	33.9		12116

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	1.67	1.73	100		0.34	7.49	23.4	1346

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	4ZYC	1.67	20	11475	576	99.84	0.2394	0.239	0.2467	RANDOM	27.286

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]
0.05	0.02		0.05		-0.07

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	40.449
r_dihedral_angle_3_deg	15.118
r_dihedral_angle_4_deg	9.644
r_dihedral_angle_1_deg	4.825
r_angle_refined_deg	1.155
r_chiral_restr	0.081
r_bond_refined_d	0.009
r_gen_planes_refined	0.007

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	743
Nucleic Acid Atoms
Solvent Atoms	62
Heterogen Atoms	41

Software

Software
Software Name	Purpose
DENZO	data reduction
SCALEPACK	data scaling
REFMAC	refinement
MOLREP	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.