4HW3

Discovery of potent Mcl-1 inhibitors using fragment-based methods and structure-based design

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	6.5	298	30% PEG3350, 0.2M MgCl2, pH 6.5, VAPOR DIFFUSION, HANGING DROP, temperature 298K

Crystal Properties
Matthews coefficient	Solvent content
2.75	55.19

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 139.446	α = 90
b = 58.76	β = 90.71
c = 140.675	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	IMAGE PLATE	MAR scanner 300 mm plate		2012-06-19	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	APS BEAMLINE 21-ID-G	0.97856	APS	21-ID-G

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (Observed)	R Sym 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	2.4	50	98.2	0.053	0.045	23.7	3.5			1	1

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	R-Sym I (Observed)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	2.4	2.44	96.3		0.299	0.364	2.55	2.7	4328

Refinement

Statistics
Diffraction ID	Structure Solution Method	Resolution (High)	Resolution (Low)	Cut-off Sigma (F)	Number Reflections (All)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (All)	R-Factor (Observed)	R-Work	R-Free	R-Free Selection Details	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	2.4	29.98	1.46	88515	88346	2001	98.23	0.2162	0.2162	0.2151	0.2628	RANDOM

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
f_dihedral_angle_d	19.612
f_angle_d	1.411
f_chiral_restr	0.08
f_bond_d	0.01
f_plane_restr	0.008

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	14358
Nucleic Acid Atoms
Solvent Atoms	251
Heterogen Atoms	300

Software

Software
Software Name	Purpose
HKL-2000	data collection
PHASER	phasing
PHENIX	refinement
HKL-2000	data reduction
HKL-2000	data scaling

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.