4FCQ

Targeting conserved water molecules: Design of 4-aryl-5-cyanopyrrolo[2,3-d]pyrimidine Hsp90 inhibitors using fragment-based screening and structure-based optimization


X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
TypeSourceAccession CodeDetails
experimental modelPDB 1UY6PDB ENTRY 1UY6

Crystallization

Crystalization Experiments
IDMethodpHTemperatureDetails
1VAPOR DIFFUSION, HANGING DROP6.529825% PEG MME 2000, 0.1M Na Cacodylate, PH6.5, 0.2M MGCl2, VAPOR DIFFUSION, HANGING DROP, temperature 298K
Crystal Properties
Matthews coefficientSolvent content
2.6653.83

Crystal Data

Unit Cell
Length ( Å )Angle ( ˚ )
a = 64.976α = 90
b = 87.957β = 90
c = 99.205γ = 90
Symmetry
Space GroupI 2 2 2

Diffraction

Diffraction Experiment
ID #Crystal IDScattering TypeData Collection TemperatureDetectorDetector TypeDetailsCollection DateMonochromatorProtocol
11x-ray100CCDADSC QUANTUM 4r2006-09-25MSINGLE WAVELENGTH
Radiation Source
ID #SourceTypeWavelength ListSynchrotron SiteBeamline
1SYNCHROTRONESRF BEAMLINE ID291.02ESRFID29

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
12.153087.40.057329071587022
Highest Resolution Shell
ID #Resolution (High)Resolution (Low)Percent Possible (All)Percent Possible (Observed)Mean I Over Sigma (Observed)RedundancyNumber Unique Reflections (All)
12.152.2284.1

Refinement

Statistics
Diffraction IDStructure Solution MethodCross Validation methodStarting modelResolution (High)Resolution (Low)Cut-off Sigma (I)Cut-off Sigma (F)Number Reflections (All)Number Reflections (Observed)Number Reflections (R-Free)Percent Reflections (Observed)R-Factor (All)R-Factor (Observed)R-WorkR-FreeR-Free Selection DetailsMean Isotropic B
X-RAY DIFFRACTIONMOLECULAR REPLACEMENTTHROUGHOUTPDB ENTRY 1UY62.15126.73223290712608124287.550.2470.193560.188130.24732RANDOM45.267
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]
0.280.17-0.45
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg37.15
r_dihedral_angle_4_deg21.168
r_dihedral_angle_3_deg16.555
r_dihedral_angle_1_deg8.192
r_angle_refined_deg2.014
r_chiral_restr0.219
r_bond_refined_d0.017
r_gen_planes_refined0.009
r_bond_other_d
r_angle_other_deg
RMS Deviations
KeyRefinement Restraint Deviation
r_dihedral_angle_2_deg37.15
r_dihedral_angle_4_deg21.168
r_dihedral_angle_3_deg16.555
r_dihedral_angle_1_deg8.192
r_angle_refined_deg2.014
r_chiral_restr0.219
r_bond_refined_d0.017
r_gen_planes_refined0.009
r_bond_other_d
r_angle_other_deg
r_gen_planes_other
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_mcbond_it
r_mcbond_other
r_mcangle_it
r_scbond_it
r_scangle_it
r_rigid_bond_restr
r_sphericity_free
r_sphericity_bonded
Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen AtomsNumber
Protein Atoms1627
Nucleic Acid Atoms
Solvent Atoms136
Heterogen Atoms21

Software

Software
Software NamePurpose
ADSCdata collection
AMoREphasing
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling