5AA9

Structure of L1198F 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

Starting Model(s)

Initial Refinement Model(s)
TypeSourceAccession CodeDetails
experimental modelPDB 4CLJPDB ENTRY 4CLJ

Crystallization

Crystalization Experiments
IDMethodpHTemperatureDetails
1VAPOR DIFFUSION, HANGING DROP8286HANGING DROP VAPOR DIFFUSION AT 13 DEGREES C. 2 MICROLITERS OF PURIFIED PROTEIN SOLUTION (11-15 MG/ML) CONTAINING INHIBITOR COMPOUND AT A 2X STOICHIOMETRY OF INHIBITOR TO PROTEIN WERE COMBINED WITH 2 MICROLITERS OF SOLUTIONS CONTAINING: 0.2 M LITHIUM SULFATE, 17-21% PEG3350 AND 0.1M TRIS PH 7.6-8.5.
Crystal Properties
Matthews coefficientSolvent content
2.141

Crystal Data

Unit Cell
Length ( Å )Angle ( ˚ )
a = 51.815α = 90
b = 57.182β = 90
c = 105.044γ = 90
Symmetry
Space GroupP 21 21 21

Diffraction

Diffraction Experiment
ID #Crystal IDScattering TypeData Collection TemperatureDetectorDetector TypeDetailsCollection DateMonochromatorProtocol
11x-ray87PIXELDECTRIS PILATUS 6M2015-04-14MSINGLE 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
11.9357.1898.70.0614.86.123916125.7
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)
11.932.1195.30.413.25.4

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 4CLJ1.9352.52238642386469476.60.2010.20.237RANDOM37
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]
-2.66-11.2113.87
RMS Deviations
KeyRefinement Restraint Deviation
c_dihedral_angle_d19.1
c_scangle_it3.45
c_scbond_it2.31
c_mcangle_it2.29
c_mcbond_it1.43
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_d19.1
c_scangle_it3.45
c_scbond_it2.31
c_mcangle_it2.29
c_mcbond_it1.43
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 Atoms2329
Nucleic Acid Atoms
Solvent Atoms181
Heterogen Atoms30

Software

Software
Software NamePurpose
CNXrefinement
autoPROCdata reduction
Aimlessdata scaling
CNXphasing