4HW2

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
2.42	49.21

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 121.997	α = 90
b = 134.327	β = 90
c = 62.043	γ = 90

Symmetry
Space Group	P 21 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	IMAGE PLATE	MAR scanner 300 mm plate		2012-07-11	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	APS BEAMLINE 21-ID-D	1.07816	APS	21-ID-D

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	2.8	50	97.7	0.047	0.057	21.7		25224	25097	2	2	4.1

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	2.8	2.85	95		0.411	0.297	3	3.4	1223

Refinement

Statistics
Diffraction ID	Structure Solution Method	Resolution (High)	Resolution (Low)	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	2.8	30	25224	25097	2490		0.2169	0.2169	0.2169	0.2452	RANDOM	51.3

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]
-0.23			-0.02		0.25

RMS Deviations
Key	Refinement Restraint Deviation
c_angle_d	1.9
c_bond_d	0.024

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	7186
Nucleic Acid Atoms
Solvent Atoms
Heterogen Atoms	190

Software

Software
Software Name	Purpose
HKL-2000	data collection
PHASER	phasing
CNS	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.