2X8D

Discovery of a Novel Class of triazolones as Checkpoint Kinase Inhibitors - Hit to Lead Exploration


X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
TypeSourceAccession CodeDetails
experimental modelPDB 1IA8PDB ENTRY 1IA8

Crystallization

Crystalization Experiments
IDMethodpHTemperatureDetails
1VAPOR DIFFUSION, HANGING DROP6.8HANGING DROP. 3UL PLUS 3UL PROTEIN: 7 MG/ML, 25MM TRIS PH7.5, 500MM NACL, 5% GLYCEROL. 5MM DTT WELL: 15-17% (W/V) PEG8000, 250MM AMMONIUM SULPHATE, 2% (V/V) GLYCEROL AND 100 MM SODIUM CACODYLATE PH 6.8
Crystal Properties
Matthews coefficientSolvent content
2.6353.21

Crystal Data

Unit Cell
Length ( Å )Angle ( ˚ )
a = 45α = 90
b = 66.236β = 94.59
c = 58.473γ = 90
Symmetry
Space GroupP 1 21 1

Diffraction

Diffraction Experiment
ID #Crystal IDScattering TypeData Collection TemperatureDetectorDetector TypeDetailsCollection DateMonochromatorProtocol
11x-ray100CCDADSC CCD2001-12-05MSINGLE WAVELENGTH
Radiation Source
ID #SourceTypeWavelength ListSynchrotron SiteBeamline
1SYNCHROTRONSRS BEAMLINE PX9.6SRSPX9.6

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
11.937.393.80.18.82.5252192
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)
11.9264.60.2431.9

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 1IA81.937.323949127093.110.16160.159980.19176RANDOM14.972
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]
-0.17-0.580.63-0.55
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg35.661
r_dihedral_angle_4_deg15.705
r_dihedral_angle_3_deg12.516
r_dihedral_angle_1_deg5.408
r_scangle_it2.75
r_scbond_it1.679
r_angle_refined_deg1.298
r_angle_other_deg1.144
r_mcangle_it1.125
r_mcbond_it0.606
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg35.661
r_dihedral_angle_4_deg15.705
r_dihedral_angle_3_deg12.516
r_dihedral_angle_1_deg5.408
r_scangle_it2.75
r_scbond_it1.679
r_angle_refined_deg1.298
r_angle_other_deg1.144
r_mcangle_it1.125
r_mcbond_it0.606
r_mcbond_other0.119
r_chiral_restr0.075
r_bond_refined_d0.011
r_gen_planes_refined0.005
r_bond_other_d0.001
r_gen_planes_other0.001
r_nbd_refined
r_nbd_other
r_nbtor_refined
r_nbtor_other
r_xyhbond_nbd_refined
r_xyhbond_nbd_other
r_metal_ion_refined
r_metal_ion_other
r_symmetry_vdw_refined
r_symmetry_vdw_other
r_symmetry_hbond_refined
r_symmetry_hbond_other
r_symmetry_metal_ion_refined
r_symmetry_metal_ion_other
r_mcangle_other
r_scbond_other
r_scangle_other
r_long_range_B_refined
r_long_range_B_other
r_rigid_bond_restr
r_sphericity_free
r_sphericity_bonded
Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen AtomsNumber
Protein Atoms2235
Nucleic Acid Atoms
Solvent Atoms352
Heterogen Atoms25

Software

Software
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing