6E1Y

Discovery of Potent 2-Aryl-6,7-Dihydro-5HPyrrolo[ 1,2-a]imidazoles as WDR5 WIN-site Inhibitors Using Fragment-Based Methods and Structure-Based Design

X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
Type	Source	Accession Code	Details
experimental model	PDB	6D9X

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	7.5	293	0.1 M Bis-Tris pH 6.0 or Hepes pH 7.5, 0.2 M ammonium acetate, 28% to 32% PEG3350

Crystal Properties
Matthews coefficient	Solvent content
2.36	47.78

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 46.971	α = 110.47
b = 61.573	β = 91.22
c = 64.668	γ = 112.27

Symmetry
Space Group	P 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	CCD	MARMOSAIC 300 mm CCD		2018-07-06	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	APS BEAMLINE 21-ID-F	0.98	APS	21-ID-F

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	1.219	50	94.1	0.04	14.68	3.3		173496

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	1.22	1.24			0.292

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Starting model	Resolution (High)	Resolution (Low)	Cut-off Sigma (F)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (Observed)	R-Work	R-Free	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	FREE R-VALUE	6D9X	1.219	29.016	1.97	173380	1983	93.94	0.1699	0.1697	0.1816

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	18.108
f_angle_d	1.113
f_chiral_restr	0.093
f_bond_d	0.008
f_plane_restr	0.007

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	4702
Nucleic Acid Atoms
Solvent Atoms	882
Heterogen Atoms

Software

Software
Software Name	Purpose
PHENIX	refinement
HKL-2000	data reduction
SCALEPACK	data scaling
AMoRE	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.