8BV2

Biological and structural analysis of new potent Integrase-LEDGF allosteric HIV-1 inhibitors

X-RAY DIFFRACTION

Starting Model(s)

Initial Refinement Model(s)
Type	Source	Accession Code	Details
experimental model	PDB	4LH4

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, SITTING DROP	6.5	293	3 microliters of protein at 5 mg/mL in 50 mM MES pH5.5, 50 mM NaCl, 5 mM DTT mixed with 3 microliters of reservoir solution containing 0.1 M sodium cacodylate pH 6.5, 1.26 M ammonium sulfate.

Crystal Properties
Matthews coefficient	Solvent content
2.49	50.6

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 72.57	α = 90
b = 72.57	β = 90
c = 65.965	γ = 120

Symmetry
Space Group	P 31 2 1

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray	120	PIXEL	DECTRIS EIGER R 4M		2021-09-15	M	SINGLE WAVELENGTH

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

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (Observed)	Rrim I (All)	Rpim I (All)	CC (Half)	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	20	100	0.0286	0.03	0.01	1	57.43	9.5		131582			29.84

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	Rrim I (All)	Rpim I (All)	CC (Half)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
1	2	2.072	100		0.1985	0.2094	0.06627	0.986	11.2	9.9

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Resolution (High)	Resolution (Low)	Cut-off Sigma (F)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (Observed)	R-Work	R-Free	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	FREE R-VALUE	2	19.97	1.34	25842	2555	98.58	0.1985	0.1955	0.2262	31.65

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]

RMS Deviations
Key	Refinement Restraint Deviation
f_dihedral_angle_d	9.227
f_angle_d	1.0241
f_chiral_restr	0.0533
f_bond_d	0.0083
f_plane_restr	0.0065

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	1020
Nucleic Acid Atoms
Solvent Atoms	102
Heterogen Atoms	35

Software

Software
Software Name	Purpose
PHENIX	refinement
XDS	data reduction
XDS	data scaling
PHASER	phasing

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 R01GM157729.