8RAK

Crystal structure of human Dihydroorotate Dehydrogenase in complex with the inhibitor 2-Hydroxy-N-(2-isopropyl-5-methyl-4-(pyridin-4-yloxy)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide

X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
Type	Source	Accession Code	Details
experimental model	PDB	7Z6C

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP		293.15	2M ammonium sulphate, 100 mM sodium acetate pH 4.8, and 30 % v/v glycerol

Crystal Properties
Matthews coefficient	Solvent content
3.51	64.99

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 91.474	α = 90
b = 91.474	β = 90
c = 124.032	γ = 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	93.15	PIXEL	DECTRIS PILATUS3 2M		2022-01-27	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	ESRF BEAMLINE ID23-2	0.8731	ESRF	ID23-2

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (Observed)	CC (Half)	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	1.85	48.83	100	0.126	0.996	9	6.6		51817			21.2

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	CC (Half)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	1.85	1.95			0.726	0.743

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	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	1.85	39.61	1.34	51746	2678	99.9	0.1655	0.1643	0.1861	25.22

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	8.0371
f_angle_d	0.929
f_chiral_restr	0.0599
f_plane_restr	0.0141
f_bond_d	0.0087

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2796
Nucleic Acid Atoms
Solvent Atoms	292
Heterogen Atoms	102

Software

Software
Software Name	Purpose
PHENIX	refinement
PHENIX	refinement
XDS	data reduction
SCALA	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 R01GM157729.