4CLI

Structure of the 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 2XP2PDB ENTRY 2XP2

Crystallization

Crystalization Experiments
IDMethodpHTemperatureDetails
1VAPOR DIFFUSION, HANGING DROP5.5286HANGING DROP VAPOR DIFFUSION AT 13 DEGREES C. EQUAL VOLUMES OF PURIFIED PROTEIN SOLUTION (APPROXIMATELY 13-15 MG/ML)CONTAINING 0.0011M INHIBITOR COMPOUND WERE COMBINED WITH A SOLUTION CONTAINING: 0.15M AMMONIUM SULFATE, 9-10.5% MONOMETHYLETHER PEG5K AND 0.1M MES IN THE PH RANGE 5.3-6.5
Crystal Properties
Matthews coefficientSolvent content
2.141

Crystal Data

Unit Cell
Length ( Å )Angle ( ˚ )
a = 51.76α = 90
b = 57.28β = 90
c = 105.02γ = 90
Symmetry
Space GroupP 21 21 21

Diffraction

Diffraction Experiment
ID #Crystal IDScattering TypeData Collection TemperatureDetectorDetector TypeDetailsCollection DateMonochromatorProtocol
11x-ray87PIXELDECTRIS PILATUS 6M2012-02-03MSINGLE WAVELENGTH
Radiation Source
ID #SourceTypeWavelength ListSynchrotron SiteBeamline
1SYNCHROTRONDIAMOND BEAMLINE I03DiamondI03

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
11.9452.5199.90.1112.66.523831116
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)
11.941.9999.80.772.86.4

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 2XP22.0552.513767735891110394.80.1990.1980.245RANDOM29.2
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]
-2.61-4.276.87
RMS Deviations
KeyRefinement Restraint Deviation
c_dihedral_angle_d19.5
c_scangle_it3.44
c_mcangle_it2.41
c_scbond_it2.36
c_mcbond_it1.49
c_angle_deg0.8
c_improper_angle_d0.66
c_bond_d0.005
c_bond_d_na
c_bond_d_prot
RMS Deviations
KeyRefinement Restraint Deviation
c_dihedral_angle_d19.5
c_scangle_it3.44
c_mcangle_it2.41
c_scbond_it2.36
c_mcbond_it1.49
c_angle_deg0.8
c_improper_angle_d0.66
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 Atoms2314
Nucleic Acid Atoms
Solvent Atoms232
Heterogen Atoms30

Software

Software
Software NamePurpose
CNXrefinement
XDSdata reduction
SCALAdata scaling
CNXphasing