6G9N

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 DROP7.22932M (NH4)2SO4 34% MPEG 2000 .02M Mercaptoethanol .1M pH=7.2 HEPES/NaOH
Crystal Properties
Matthews coefficientSolvent content
2.346.55

Crystal Data

Unit Cell
Length ( Å )Angle ( ˚ )
a = 48.904α = 90
b = 70.324β = 110.38
c = 60.747γ = 90
Symmetry
Space GroupP 1 21 1

Diffraction

Diffraction Experiment
ID #Crystal IDScattering TypeData Collection TemperatureDetectorDetector TypeDetailsCollection DateMonochromatorProtocol
11x-ray100PIXELDECTRIS PILATUS 300K2016-01-28MSINGLE WAVELENGTH
Radiation Source
ID #SourceTypeWavelength ListSynchrotron SiteBeamline
1ROTATING ANODERIGAKU FR-X1.54178

Data Collection

Overall
ID #Resolution (High)Resolution (Low)Percent Possible (Observed)Rrim I (All)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
11.7628.2598.20.03122.52.73753325.08
Highest Resolution Shell
ID #Resolution (High)Resolution (Low)Percent Possible (All)Percent Possible (Observed)Rrim I (All)Mean I Over Sigma (Observed)RedundancyNumber Unique Reflections (All)
11.761.8190.40.528

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 SYNTHESISTHROUGHOUT1.7628.2537286191897.30.1680.1650.218RANDOM31.364
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]
1.32062.0421-1.80110.4805
RMS Deviations
KeyRefinement Restraint Deviation
t_other_torsion15.76
t_omega_torsion6.13
t_angle_deg1.08
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_torsion15.76
t_omega_torsion6.13
t_angle_deg1.08
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 Atoms2802
Nucleic Acid Atoms
Solvent Atoms558
Heterogen Atoms79

Software

Software
Software NamePurpose
BUSTERrefinement
XDSdata reduction
Aimlessdata scaling
BUSTERphasing