2X8I

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 2X8DPDB ENTRY 2X8D

Crystallization

Crystalization Experiments
IDMethodpHTemperatureDetails
1VAPOR DIFFUSION, HANGING DROP6.5HANGING DROP 3 UL PLUS 3UL PROTEIN: 7MG/ML, 2MM COMPOUND, 25MM TRIS PH7.5, 500MM NACL, 5% GLYCEROL. 5MM DTT WELL: 16-22% (W/V) PEG3350, 150MM AMMONIUM SULPHATE AND 100 MM BES PH 6.5
Crystal Properties
Matthews coefficientSolvent content
2.2845.65

Crystal Data

Unit Cell
Length ( Å )Angle ( ˚ )
a = 41.255α = 90
b = 70.9β = 90
c = 104.241γ = 90
Symmetry
Space GroupP 21 21 21

Diffraction

Diffraction Experiment
ID #Crystal IDScattering TypeData Collection TemperatureDetectorDetector TypeDetailsCollection DateMonochromatorProtocol
11x-ray100CCDMARRESEARCH2002-08-20MSINGLE 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
11.9231.1694.30.08145.8225302
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)
11.922.0289.40.295.65.4

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 2X8D1.9231.1621383114793.590.18940.18760.22368RANDOM15.693
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]
-1.491.65-0.17
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg37.479
r_dihedral_angle_4_deg15.719
r_dihedral_angle_3_deg12.344
r_dihedral_angle_1_deg5.158
r_scangle_it2.124
r_angle_other_deg1.825
r_scbond_it1.275
r_angle_refined_deg1.269
r_mcangle_it0.937
r_mcbond_it0.503
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg37.479
r_dihedral_angle_4_deg15.719
r_dihedral_angle_3_deg12.344
r_dihedral_angle_1_deg5.158
r_scangle_it2.124
r_angle_other_deg1.825
r_scbond_it1.275
r_angle_refined_deg1.269
r_mcangle_it0.937
r_mcbond_it0.503
r_chiral_restr0.157
r_mcbond_other0.077
r_bond_refined_d0.007
r_gen_planes_refined0.004
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 Atoms2091
Nucleic Acid Atoms
Solvent Atoms241
Heterogen Atoms38

Software

Software
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing