3R21

Design, synthesis, and biological evaluation of pyrazolopyridine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (Part I)

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP	9	298	10% Peg550 MME, 100mM Tris, 10% ethylene glycol, pH 9, VAPOR DIFFUSION, SITTING DROP, temperature 298K

Crystal Properties
Matthews coefficient	Solvent content
2.58	52.29

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 82.21	α = 90
b = 82.21	β = 90
c = 165.7	γ = 120

Symmetry
Space Group	P 61 2 2

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray	193	CCD	RAYONIX MX225HE	Diamond(111)monochromator	2008-06-11	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	APS BEAMLINE 31-ID	0.9793	APS	31-ID

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (Observed)	Net I Over Average Sigma (I)	Redundancy	Number Reflections (All)	Number Reflections (Observed)	Observed Criterion Sigma (F)	Observed Criterion Sigma (I)	B (Isotropic) From Wilson Plot
1	2.9	50	99.8	0.063	40.2	10		7898	2	2	90.8268

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	2.9	3	100		0.696	2.9	10.3	754

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Starting model	Resolution (High)	Resolution (Low)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (Observed)	R-Work	R-Free	R-Free Selection Details	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	THROUGHOUT	pdb entry 2W1C	2.9	25	7427	357	99.31	0.26	0.258	0.30467	RANDOM	81.871

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]
-0.03			-0.03		0.07

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	33.213
r_dihedral_angle_4_deg	21.906
r_dihedral_angle_3_deg	21.426
r_dihedral_angle_1_deg	7.38
r_scangle_it	3.333
r_scbond_it	1.981
r_angle_refined_deg	1.805
r_mcangle_it	1.545
r_mcbond_it	0.847
r_chiral_restr	0.111

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	33.213
r_dihedral_angle_4_deg	21.906
r_dihedral_angle_3_deg	21.426
r_dihedral_angle_1_deg	7.38
r_scangle_it	3.333
r_scbond_it	1.981
r_angle_refined_deg	1.805
r_mcangle_it	1.545
r_mcbond_it	0.847
r_chiral_restr	0.111
r_bond_refined_d	0.018
r_gen_planes_refined	0.007

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2074
Nucleic Acid Atoms
Solvent Atoms
Heterogen Atoms	32

Software

Software
Software Name	Purpose
ADSC	data collection
PHASER	phasing
REFMAC	refinement
HKL-2000	data reduction
HKL-2000	data scaling

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.