8A27

EGFR kinase domain in complex with 2-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-1-yl)-2-[6-[2-[4-[[4-(hydroxymethyl)-1-piperidyl]methyl]phenyl]ethynyl]-1-oxo-4-(trifluoromethyl)isoindolin-2-yl]-N-thiazol-2-yl-acetamide

X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
Type	Source	Accession Code	Details
experimental model	PDB	5HG8

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP	6	293	20% PEG Smear Medium, 0.1M MES, 0.15 ammonium nitrate, 5% ethylene glycol

Crystal Properties
Matthews coefficient	Solvent content
1.84	32.98

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 119.28	α = 90
b = 34.915	β = 128.92
c = 84.334	γ = 90

Symmetry
Space Group	C 1 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 6M		2019-09-02	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	SLS BEAMLINE X10SA	0.9999	SLS	X10SA

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (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	1.07	65.61	92.5	1	13.1	5		86262

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	CC (Half)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	1.07	1.16			0.66

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	5hg8	1.07	65.61	86262	4541	76.45	0.1262	0.1244	0.1599	RANDOM	16.31

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]
0.34		0.03	-0.04		-0.15

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	33.713
r_dihedral_angle_4_deg	18.3
r_dihedral_angle_3_deg	12.78
r_dihedral_angle_1_deg	6.27
r_rigid_bond_restr	6.127
r_angle_refined_deg	2.082
r_angle_other_deg	1.552
r_chiral_restr	0.126
r_bond_refined_d	0.018
r_gen_planes_refined	0.011

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	33.713
r_dihedral_angle_4_deg	18.3
r_dihedral_angle_3_deg	12.78
r_dihedral_angle_1_deg	6.27
r_rigid_bond_restr	6.127
r_angle_refined_deg	2.082
r_angle_other_deg	1.552
r_chiral_restr	0.126
r_bond_refined_d	0.018
r_gen_planes_refined	0.011
r_bond_other_d	0.003
r_gen_planes_other	0.001

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2159
Nucleic Acid Atoms
Solvent Atoms	371
Heterogen Atoms	72

Software

Software
Software Name	Purpose
REFMAC	refinement
PDB_EXTRACT	data extraction
XDS	data reduction
STARANISO	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.