4CLJ

Structure of L1196M Mutant Human Anaplastic Lymphoma Kinase in Complex with PF-06463922 ((10R)-7-amino-12-fluoro-2,10,16-trimethyl- 15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo(4,3-h)(2,5,11) benzoxadiazacyclotetradecine-3-carbonitrile).


X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
IDMethodpHTemperatureDetails
1VAPOR DIFFUSION, HANGING DROP8.5286HANGING DROP VAPOR DIFFUSION AT 13 DEGREES C. EQUAL VOLUMES OF PURIFIED PROTEIN SOLUTION (APPROXIMATELY 11.3 MG/ML)CONTAINING 0.9 MM INHIBITOR COMPOUND WERE COMBINED WITH A SOLUTION CONTAINING: 0.2 M LITHIUM SULFATE, 18% PEG5K AND 0.1M TRIS PH 8.5.
Crystal Properties
Matthews coefficientSolvent content
2.141

Crystal Data

Unit Cell
Length ( Å )Angle ( ˚ )
a = 51.754α = 90
b = 57.587β = 90
c = 104.887γ = 90
Symmetry
Space GroupP 21 21 21

Diffraction

Diffraction Experiment
ID #Crystal IDScattering TypeData Collection TemperatureDetectorDetector TypeDetailsCollection DateMonochromatorProtocol
11x-ray87PIXELDECTRIS PILATUS 6M2006-06-20MSINGLE WAVELENGTH
Radiation Source
ID #SourceTypeWavelength ListSynchrotron SiteBeamline
1SYNCHROTRONAPS BEAMLINE 17-IDAPS17-ID

Data Collection

Overall
ID #Resolution (High)Resolution (Low)Percent Possible (Observed)R Merge I (Observed)Net I Over Average Sigma (I)RedundancyNumber Reflections (All)Number Reflections (Observed)Observed Criterion Sigma (F)Observed Criterion Sigma (I)B (Isotropic) From Wilson Plot
11.66104.8996.70.0520.46.136453122.9
Highest Resolution Shell
ID #Resolution (High)Resolution (Low)Percent Possible (All)Percent Possible (Observed)R Merge I (Observed)Mean I Over Sigma (Observed)RedundancyNumber Unique Reflections (All)
11.661.7580.40.472.84.2

Refinement

Statistics
Diffraction IDStructure Solution MethodCross Validation methodStarting modelResolution (High)Resolution (Low)Number Reflections (All)Number Reflections (Observed)Number Reflections (R-Free)Percent Reflections (Observed)R-Factor (Observed)R-WorkR-FreeR-Free Selection DetailsMean Isotropic B
X-RAY DIFFRACTIONMOLECULAR REPLACEMENTTHROUGHOUTPDB ENTRY 2XP21.6652.443639336393110596.20.1970.1960.229RANDOM26
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]
-3.82-2.886.7
RMS Deviations
KeyRefinement Restraint Deviation
c_dihedral_angle_d18.3
c_scangle_it3.28
c_scbond_it2.22
c_mcangle_it2.03
c_mcbond_it1.3
c_angle_deg0.8
c_improper_angle_d0.65
c_bond_d0.005
c_bond_d_na
c_bond_d_prot
RMS Deviations
KeyRefinement Restraint Deviation
c_dihedral_angle_d18.3
c_scangle_it3.28
c_scbond_it2.22
c_mcangle_it2.03
c_mcbond_it1.3
c_angle_deg0.8
c_improper_angle_d0.65
c_bond_d0.005
c_bond_d_na
c_bond_d_prot
c_angle_d
c_angle_d_na
c_angle_d_prot
c_angle_deg_na
c_angle_deg_prot
c_dihedral_angle_d_na
c_dihedral_angle_d_prot
c_improper_angle_d_na
c_improper_angle_d_prot
Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen AtomsNumber
Protein Atoms2324
Nucleic Acid Atoms
Solvent Atoms339
Heterogen Atoms30

Software

Software
Software NamePurpose
CNXrefinement
autoPROCdata reduction
SCALAdata scaling
CNXphasing