3EN4

Targeted polypharmacology: crystal structure of the c-Src kinase domain in complex with PP121, a multitargeted kinase inhibitor


X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
TypeSourceAccession CodeDetails
experimental modelPDB 1YOJPDB entry 1YOJ, CHAIN A

Crystallization

Crystalization Experiments
IDMethodpHTemperatureDetails
1VAPOR DIFFUSION, HANGING DROP829814 mg/mL kinase, 50 mM Tris-HCl, 100 mM NaCl, 5% (v/v) glycerol mixed 1:1 with 20% (w/v) glycerol precipitant well solution, pH 8.0, vapor diffusion, hanging drop, temperature 298K
Crystal Properties
Matthews coefficientSolvent content
2.9758.58

Crystal Data

Unit Cell
Length ( Å )Angle ( ˚ )
a = 42.37α = 100.63
b = 63.143β = 88.68
c = 73.938γ = 90.4
Symmetry
Space GroupP 1

Diffraction

Diffraction Experiment
ID #Crystal IDScattering TypeData Collection TemperatureDetectorDetector TypeDetailsCollection DateMonochromatorProtocol
11x-ray100CCDADSC QUANTUM 3152007-07-01MSINGLE WAVELENGTH
Radiation Source
ID #SourceTypeWavelength ListSynchrotron SiteBeamline
1SYNCHROTRONALS BEAMLINE 8.2.11.000ALS8.2.1

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
12.555098.40.10112.4143.823940
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)
12.552.64950.4723.3

Refinement

Statistics
Diffraction IDStructure Solution MethodCross Validation methodStarting modelResolution (High)Resolution (Low)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 1YOJ, CHAIN A2.5542.3622721121798.040.20130.198470.25457RANDOM24.882
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]
0.01-0.01-0.010.01-0.01
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg36.437
r_dihedral_angle_4_deg17.019
r_dihedral_angle_3_deg14.636
r_dihedral_angle_1_deg5.723
r_scangle_it2.851
r_scbond_it1.793
r_angle_refined_deg1.339
r_mcangle_it0.869
r_mcbond_it0.44
r_nbtor_refined0.305
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg36.437
r_dihedral_angle_4_deg17.019
r_dihedral_angle_3_deg14.636
r_dihedral_angle_1_deg5.723
r_scangle_it2.851
r_scbond_it1.793
r_angle_refined_deg1.339
r_mcangle_it0.869
r_mcbond_it0.44
r_nbtor_refined0.305
r_nbd_refined0.198
r_symmetry_vdw_refined0.175
r_xyhbond_nbd_refined0.156
r_symmetry_hbond_refined0.091
r_chiral_restr0.085
r_bond_refined_d0.011
r_gen_planes_refined0.006
r_bond_other_d
r_angle_other_deg
r_gen_planes_other
r_nbd_other
r_nbtor_other
r_xyhbond_nbd_other
r_metal_ion_refined
r_metal_ion_other
r_symmetry_vdw_other
r_symmetry_hbond_other
r_symmetry_metal_ion_refined
r_symmetry_metal_ion_other
r_mcbond_other
r_rigid_bond_restr
r_sphericity_free
r_sphericity_bonded
Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen AtomsNumber
Protein Atoms4040
Nucleic Acid Atoms
Solvent Atoms6
Heterogen Atoms48

Software

Software
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling