8A2D

EGFR kinase domain (L858R/V948R) in complex with 2-[4-(difluoromethyl)-6-[2-[4-[[4-(hydroxymethyl)-1-piperidyl]methyl]phenyl]ethynyl]-7-methyl-indazol-2-yl]-2-spiro[6,7-dihydropyrrolo[1,2-c]imidazole-5,1'-cyclopropane]-1-yl-N-thiazol-2-yl-acetamide

X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
Type	Source	Accession Code	Details
experimental model	PDB	8A27

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP	6.5	293	20% PEG Smear High, 0.1M MES

Crystal Properties
Matthews coefficient	Solvent content
1.8	31.79

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 119.619	α = 90
b = 34.951	β = 128.81
c = 83.934	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		2020-09-12	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	1.11	65.4	90.3	1	11.2	3.6		90192

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	1.12	1.16			0.67

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	8A27	1.11	65.4	90192	4722	89.67	0.164	0.1632	0.1788	RANDOM	15.73

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]
0.14		0.09	-0.33		0.02

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	34.572
r_dihedral_angle_4_deg	17.761
r_dihedral_angle_3_deg	14.141
r_dihedral_angle_1_deg	6.42
r_angle_refined_deg	2.278
r_angle_other_deg	1.54
r_chiral_restr	0.133
r_bond_refined_d	0.021
r_gen_planes_refined	0.013
r_bond_other_d	0.001

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	34.572
r_dihedral_angle_4_deg	17.761
r_dihedral_angle_3_deg	14.141
r_dihedral_angle_1_deg	6.42
r_angle_refined_deg	2.278
r_angle_other_deg	1.54
r_chiral_restr	0.133
r_bond_refined_d	0.021
r_gen_planes_refined	0.013
r_bond_other_d	0.001
r_gen_planes_other	0.001

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2276
Nucleic Acid Atoms
Solvent Atoms	387
Heterogen Atoms	65

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.