6FMD

Targeting myeloid differentiation using potent human dihydroorotate dehydrogenase (hDHODH) inhibitors based on 2-hydroxypyrazolo[1,5-a]pyridine scaffold

X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
Type	Source	Accession Code	Details
experimental model	PDB	5MUT

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	5.2	293	0.2M KBr, 0.2M KSCN, 0.1M NaAc pH 5.2, 25% PEG 400, 2% PGA-LM

Crystal Properties
Matthews coefficient	Solvent content
3.37	63.47

Crystal Data

Unit Cell
Length ( ? )	Angle ( ? )
a = 90.441	�� = 90
b = 90.441	�� = 90
c = 122.446	�� = 120

Symmetry
Space Group	P 32 2 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	PIXEL	DECTRIS PILATUS 2M		2017-04-08	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	ESRF BEAMLINE ID23-1	0.97242	ESRF	ID23-1

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Sym I (Observed)	Rrim I (All)	Rpim I (All)	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	1.58	78.324	99.6	0.071	0.08	0.036	11	4.6		79465

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	R-Sym I (Observed)	Rrim I (All)	Rpim I (All)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	1.58	1.67	99.7		0.74	0.74	0.835	0.38	1	4.7

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	5MUT	1.58	78.32	75404	4016	99.53	0.138	0.1368	0.1597	RANDOM	26.408

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
r_dihedral_angle_2_deg	36.175
r_sphericity_free	30.319
r_dihedral_angle_4_deg	17.739
r_sphericity_bonded	14.134
r_dihedral_angle_3_deg	11.341
r_dihedral_angle_1_deg	5.446
r_rigid_bond_restr	2.462
r_angle_refined_deg	1.647
r_angle_other_deg	1.016
r_chiral_restr	0.096

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	36.175
r_sphericity_free	30.319
r_dihedral_angle_4_deg	17.739
r_sphericity_bonded	14.134
r_dihedral_angle_3_deg	11.341
r_dihedral_angle_1_deg	5.446
r_rigid_bond_restr	2.462
r_angle_refined_deg	1.647
r_angle_other_deg	1.016
r_chiral_restr	0.096
r_bond_refined_d	0.014
r_gen_planes_refined	0.01
r_bond_other_d	0.002
r_gen_planes_other	0.002

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2731
Nucleic Acid Atoms
Solvent Atoms	155
Heterogen Atoms	181

Software

Software
Software Name	Purpose
REFMAC	refinement
MOSFLM	data reduction
SCALA	data scaling
PHASER	phasing
PDB_EXTRACT	data extraction

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.