6W35 | pdb_00006w35

A new Autotaxin Inhibitor for the Treatment of Idiopathic Pulmonary Fibrosis: A Clinical Candidate Discovered Using DNA-Encoded Chemistry

X-RAY DIFFRACTION

Starting Model(s)

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

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP		293	17.50% (w/v) PEG 3350, 0.50 M NaSCN, 0.15 M NH4I

Crystal Properties
Matthews coefficient	Solvent content
2.84	56.67

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 75.723	α = 90
b = 77.377	β = 112.11
c = 94.433	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	PIXEL	DECTRIS PILATUS3 S 6M		2019-06-15	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	SLS BEAMLINE X10SA	0.99983	SLS	X10SA

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (Observed)	Rrim I (All)	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	1.98	87.49	95.6	0.055	0.07	0.998	12.86	2.4		67503			37.274

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	Rrim I (All)	CC (Half)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	1.98	2.23	97		0.451	0.024	0.787	2.43	2.4

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 (Depositor)	R-Work (DCC)	R-Free (Depositor)	R-Free (DCC)	R-Free Selection Details	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	THROUGHOUT	5MHP	1.98	87.49	65575	1928	95.76	0.1801	0.1786	0.19	0.2303	0.24	RANDOM	39.139

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]
-0.37		-0.19	-0.24		0.57

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	34.682
r_dihedral_angle_4_deg	15.913
r_dihedral_angle_3_deg	12.284
r_dihedral_angle_1_deg	6.475
r_angle_other_deg	2.768
r_angle_refined_deg	1.595
r_chiral_restr	0.114
r_gen_planes_other	0.017
r_bond_refined_d	0.012
r_gen_planes_refined	0.008

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	6410
Nucleic Acid Atoms
Solvent Atoms	518
Heterogen Atoms	171

Software

Software
Software Name	Purpose
REFMAC	refinement
XDS	data reduction
XSCALE	data scaling
PDB_EXTRACT	data extraction
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.