6G93

Fragment-based discovery of a highly potent, orally bioavailable inhibitor which modulates the phosphorylation and catalytic activity of ERK1/2


X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
IDMethodpHTemperatureDetails
1VAPOR DIFFUSION, SITTING DROP7.22930.1M HEPES/NaOHpH=7.2, 34.0%w/v MPEG 2000, 0.02M Mercaptoethanol, 0.2M (NH4)2SO4
Crystal Properties
Matthews coefficientSolvent content
2.3146.84

Crystal Data

Unit Cell
Length ( Å )Angle ( ˚ )
a = 48.812α = 90
b = 70.514β = 110.3
c = 60.994γ = 90
Symmetry
Space GroupP 1 21 1

Diffraction

Diffraction Experiment
ID #Crystal IDScattering TypeData Collection TemperatureDetectorDetector TypeDetailsCollection DateMonochromatorProtocol
11x-ray100PIXELDECTRIS PILATUS 6M-F2014-12-01MSINGLE WAVELENGTH
Radiation Source
ID #SourceTypeWavelength ListSynchrotron SiteBeamline
1SYNCHROTRONDIAMOND BEAMLINE I020.97944DiamondI02

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
11.6743.9599.70.0319.43.34550131.71
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)
11.671.6899.81.166

Refinement

Statistics
Diffraction IDStructure Solution MethodCross Validation methodResolution (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 DIFFRACTIONFOURIER SYNTHESISTHROUGHOUT1.6743.9545237231399.70.1730.1710.213RANDOM42.519
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]
0.70771.6614-1.15630.4486
RMS Deviations
KeyRefinement Restraint Deviation
t_other_torsion14.7
t_omega_torsion6.23
t_angle_deg1.11
t_bond_d0.013
t_dihedral_angle_d
t_incorr_chiral_ct
t_pseud_angle
t_trig_c_planes
t_gen_planes
t_it
RMS Deviations
KeyRefinement Restraint Deviation
t_other_torsion14.7
t_omega_torsion6.23
t_angle_deg1.11
t_bond_d0.013
t_dihedral_angle_d
t_incorr_chiral_ct
t_pseud_angle
t_trig_c_planes
t_gen_planes
t_it
t_nbd
t_improper_torsion
t_chiral_improper_torsion
t_sum_occupancies
t_utility_distance
t_utility_angle
t_utility_torsion
t_ideal_dist_contact
Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen AtomsNumber
Protein Atoms2790
Nucleic Acid Atoms
Solvent Atoms402
Heterogen Atoms59

Software

Software
Software NamePurpose
BUSTERrefinement
XDSdata reduction
Aimlessdata scaling
BUSTERphasing