4LEK

Structure-Based Design of New Dihydrofolate Reductase Antibacterial Agents: 7-(Benzimidazol-1-yl)-2,4-diaminoquinazolines

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	7.2	298	PEG 4000, sodium acetate, pH 7.2, VAPOR DIFFUSION, HANGING DROP, temperature 298K

Crystal Properties
Matthews coefficient	Solvent content
2.52	51.28

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 79.346	α = 90
b = 79.346	β = 90
c = 107.496	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	100	IMAGE PLATE	MAR scanner 345 mm plate			M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	ROTATING ANODE	RIGAKU	1.5418

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (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	1.7	21.072					21377

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	MOLECULAR REPLACEMENT	THROUGHOUT	1.7	22.25	21377	1155	99.47	0.2032	0.2024	0.218	RANDOM	22.559

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	-0.01		-0.03		0.04

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	34.361
r_dihedral_angle_4_deg	18.392
r_dihedral_angle_3_deg	12.199
r_dihedral_angle_1_deg	5.688
r_angle_refined_deg	1.585
r_scangle_it	1.178
r_scbond_it	0.789
r_mcangle_it	0.478
r_nbtor_refined	0.303
r_mcbond_it	0.301

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	34.361
r_dihedral_angle_4_deg	18.392
r_dihedral_angle_3_deg	12.199
r_dihedral_angle_1_deg	5.688
r_angle_refined_deg	1.585
r_scangle_it	1.178
r_scbond_it	0.789
r_mcangle_it	0.478
r_nbtor_refined	0.303
r_mcbond_it	0.301
r_symmetry_vdw_refined	0.19
r_nbd_refined	0.169
r_symmetry_hbond_refined	0.153
r_xyhbond_nbd_refined	0.083
r_chiral_restr	0.068
r_bond_refined_d	0.007
r_gen_planes_refined	0.003

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	1272
Nucleic Acid Atoms
Solvent Atoms	105
Heterogen Atoms	78

Software

Software
Software Name	Purpose
MOSFLM	data reduction
SCALEPACK	data scaling
PHASER	phasing
REFMAC	refinement
PDB_EXTRACT	data extraction

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), 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.