5UVC

Design, Synthesis, and Evaluation of the First Selective and Potent G-protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP	5.9	273	18% PEG MME 2000, 100mM MES pH 5.9, 17.5mM Ammonium Sulfate

Crystal Properties
Matthews coefficient	Solvent content
2.42	49.08

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 113.157	α = 90
b = 113.157	β = 90
c = 95.427	γ = 90

Symmetry
Space Group	P 42 21 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	ADSC QUANTUM 315		2005-09-16	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	ALS BEAMLINE 5.0.2	1.0	ALS	5.0.2

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	2.65	50	99.9	0.115	9	5.7		18606

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	2.65	2.74	98.8		0.524		4.8	1791

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		THROUGHOUT	2.65	30	17607	948	99.61	0.2167	0.2145	0.2603	RANDOM	60.002

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]
0.98			0.98		-1.95

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	33.602
r_dihedral_angle_4_deg	16.085
r_dihedral_angle_3_deg	14.988
r_dihedral_angle_1_deg	6.112
r_angle_refined_deg	0.986
r_angle_other_deg	0.759
r_chiral_restr	0.057
r_bond_refined_d	0.008
r_gen_planes_refined	0.004
r_bond_other_d	0.001

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	33.602
r_dihedral_angle_4_deg	16.085
r_dihedral_angle_3_deg	14.988
r_dihedral_angle_1_deg	6.112
r_angle_refined_deg	0.986
r_angle_other_deg	0.759
r_chiral_restr	0.057
r_bond_refined_d	0.008
r_gen_planes_refined	0.004
r_bond_other_d	0.001
r_gen_planes_other	0.001

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	3736
Nucleic Acid Atoms
Solvent Atoms	72
Heterogen Atoms	39

Software

Software
Software Name	Purpose
REFMAC	refinement
HKL-2000	data reduction
HKL-2000	data scaling
PHASER	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 R01GM133198.