3D62

Development of Broad-Spectrum Halomethyl Ketone Inhibitors Against Coronavirus Main Protease 3CLpro

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	7	298	0.7 M sodium malonate (pH 7.0), and 3-5% isopropanol, VAPOR DIFFUSION, HANGING DROP, temperature 298K

Crystal Properties
Matthews coefficient	Solvent content
1.96	37.17

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 106.668	α = 90
b = 45.16	β = 90
c = 53.967	γ = 90

Symmetry
Space Group	P 21 21 2

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray		CCD	ADSC QUANTUM 210	Monochromator:Si (111) channel cut monochromator; mirror: oxford Danfysik toroidal focusing mirror	2007-06-07	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	SYNCHROTRON	NSLS BEAMLINE X6A	0.9537	NSLS	X6A

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Sym 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	2.7	50	98.8	0.077	11.3	5		7556

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R-Sym I (Observed)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	2.7	2.8	98.4		0.505		5.7	719

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	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		THROUGHOUT	2.7	34.46	7510	372	98.89	0.264	0.259	0.363	RANDOM	37.002

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]
-0.55			1.86		-1.31

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	38.257
r_dihedral_angle_4_deg	18.738
r_dihedral_angle_3_deg	17.962
r_dihedral_angle_1_deg	6.065
r_angle_refined_deg	1.112
r_scangle_it	0.884
r_scbond_it	0.693
r_mcangle_it	0.476
r_mcbond_it	0.313
r_nbtor_refined	0.304

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	38.257
r_dihedral_angle_4_deg	18.738
r_dihedral_angle_3_deg	17.962
r_dihedral_angle_1_deg	6.065
r_angle_refined_deg	1.112
r_scangle_it	0.884
r_scbond_it	0.693
r_mcangle_it	0.476
r_mcbond_it	0.313
r_nbtor_refined	0.304
r_symmetry_hbond_refined	0.243
r_nbd_refined	0.211
r_xyhbond_nbd_refined	0.178
r_symmetry_vdw_refined	0.172
r_chiral_restr	0.074
r_bond_refined_d	0.009
r_gen_planes_refined	0.003

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2322
Nucleic Acid Atoms
Solvent Atoms	53
Heterogen Atoms	15

Software

Software
Software Name	Purpose
REFMAC	refinement
PDB_EXTRACT	data extraction
Blu-Ice	data collection
DENZO	data reduction
SCALEPACK	data scaling
HKL-2000	data scaling
AMoRE	phasing

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.