8BR7

Discovery of IRAK4 Inhibitors BAY1834845 and BAY1830839


X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
IDMethodpHTemperatureDetails
1VAPOR DIFFUSION, HANGING DROP2930.1M sodium acetate buffer at pH 4.9, 1.5-1.7M ammonium citrate and 0.02M hexaaminecobalt(III)chloride
Crystal Properties
Matthews coefficientSolvent content
2.754.5

Crystal Data

Unit Cell
Length ( Å )Angle ( ˚ )
a = 87.258α = 90
b = 117.97β = 90
c = 139.861γ = 90
Symmetry
Space GroupI 2 2 2

Diffraction

Diffraction Experiment
ID #Crystal IDScattering TypeData Collection TemperatureDetectorDetector TypeDetailsCollection DateMonochromatorProtocol
11x-ray100PIXELDECTRIS EIGER X 16M2021-10-04MSINGLE WAVELENGTH
Radiation Source
ID #SourceTypeWavelength ListSynchrotron SiteBeamline
1SYNCHROTRONPETRA III, EMBL c/o DESY BEAMLINE P14 (MX2)0.9763PETRA III, EMBL c/o DESYP14 (MX2)

Data Collection

Overall
ID #Resolution (High)Resolution (Low)Percent Possible (Observed)Rrim I (All)CC (Half)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
12.11919.7786.20.1150.99916.696.4935635
Highest Resolution Shell
ID #Resolution (High)Resolution (Low)Percent Possible (All)Percent Possible (Observed)CC (Half)Mean I Over Sigma (Observed)RedundancyNumber Unique Reflections (All)
12.122.250.7011.66

Refinement

Statistics
Diffraction IDStructure Solution MethodCross Validation methodStarting modelResolution (High)Resolution (Low)Number Reflections (Observed)Number Reflections (R-Free)Percent Reflections (Observed)R-Factor (All)R-WorkR-FreeMean Isotropic B
X-RAY DIFFRACTIONMOLECULAR REPLACEMENTTHROUGHOUTin house model2.11919.76835633178286.1760.2410.23870.287960.235
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]
-1.0594.994-3.935
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg34.303
r_dihedral_angle_4_deg19.593
r_dihedral_angle_3_deg14.972
r_lrange_other14.255
r_lrange_it14.24
r_scangle_it11.666
r_scangle_other11.639
r_mcangle_it9.914
r_mcangle_other9.913
r_scbond_it8.016
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg34.303
r_dihedral_angle_4_deg19.593
r_dihedral_angle_3_deg14.972
r_lrange_other14.255
r_lrange_it14.24
r_scangle_it11.666
r_scangle_other11.639
r_mcangle_it9.914
r_mcangle_other9.913
r_scbond_it8.016
r_scbond_other7.999
r_mcbond_it7.269
r_mcbond_other7.267
r_dihedral_angle_1_deg5.993
r_angle_refined_deg1.239
r_angle_other_deg1.11
r_symmetry_xyhbond_nbd_refined0.26
r_symmetry_nbd_refined0.239
r_nbd_other0.221
r_nbd_refined0.185
r_symmetry_nbd_other0.177
r_nbtor_refined0.156
r_xyhbond_nbd_refined0.134
r_xyhbond_nbd_other0.105
r_symmetry_nbtor_other0.074
r_chiral_restr0.044
r_symmetry_xyhbond_nbd_other0.025
r_bond_refined_d0.004
r_gen_planes_refined0.004
r_bond_other_d0.001
r_gen_planes_other0.001
Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen AtomsNumber
Protein Atoms4344
Nucleic Acid Atoms
Solvent Atoms41
Heterogen Atoms76

Software

Software
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
MOLREPphasing