2X8E

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


X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
IDMethodpHTemperatureDetails
1VAPOR DIFFUSION, HANGING DROP6.5HANGING DROP 3UL PLUS 3UL PROTEIN: 7 MG/ML, 25MM TRIS PH7.5, 500MM NACL, 5% GLYCEROL, 5MM DTT, 2MM COMPOUND WELL: 12-16% (W/V) PEG3350, 100-200MM AMMONIUM SULPHATE, 2% (V/V) GLYCEROL AND 100 MM SODIUM CACODYLATE PH 6.5
Crystal Properties
Matthews coefficientSolvent content
2.4850.5

Crystal Data

Unit Cell
Length ( Å )Angle ( ˚ )
a = 45.055α = 90
b = 65.858β = 101.73
c = 54.468γ = 90
Symmetry
Space GroupP 1 21 1

Diffraction

Diffraction Experiment
ID #Crystal IDScattering TypeData Collection TemperatureDetectorDetector TypeDetailsCollection DateMonochromatorProtocol
11x-ray100CCDMARRESEARCH SX-1652002-11-23MSINGLE WAVELENGTH
Radiation Source
ID #SourceTypeWavelength ListSynchrotron SiteBeamline
1SYNCHROTRONEMBL/DESY, HAMBURG BEAMLINE X13EMBL/DESY, HAMBURGX13

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
12.516.5572.50.115.42.675592
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)
12.52.6426.30.2721.7

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 2X8D2.516.51718737269.680.235470.231850.30865RANDOM42.257
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]
-3.331.811.972.1
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg40.042
r_dihedral_angle_4_deg21.374
r_dihedral_angle_3_deg18.202
r_dihedral_angle_1_deg6.776
r_scangle_it1.982
r_angle_refined_deg1.531
r_scbond_it1.223
r_mcangle_it0.951
r_angle_other_deg0.93
r_mcbond_it0.516
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg40.042
r_dihedral_angle_4_deg21.374
r_dihedral_angle_3_deg18.202
r_dihedral_angle_1_deg6.776
r_scangle_it1.982
r_angle_refined_deg1.531
r_scbond_it1.223
r_mcangle_it0.951
r_angle_other_deg0.93
r_mcbond_it0.516
r_mcbond_other0.079
r_chiral_restr0.078
r_bond_refined_d0.011
r_gen_planes_refined0.007
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 Atoms2054
Nucleic Acid Atoms
Solvent Atoms63
Heterogen Atoms31

Software

Software
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing