PDB-8dxe: HIV-1 reverse transcriptase/rilpivirine with bound fragment 2-ami...

ID or keywords:

Entry

Database: PDB / ID: 8dxe

Title

HIV-1 reverse transcriptase/rilpivirine with bound fragment 2-amino-6-fluorobenzonitrile at the NNRTI adjacent site

Components

Reverse transcriptase/ribonuclease H
p51 RT

Keywords

TRANSFERASE / HIV-1 reverse transcriptase

Function / homology

Function and homology information

HIV-1 retropepsin / symbiont-mediated activation of host apoptosis / retroviral ribonuclease H / exoribonuclease H / exoribonuclease H activity / host multivesicular body / DNA integration / viral genome integration into host DNA / RNA-directed DNA polymerase / establishment of integrated proviral latency ...
Similarity search - Function

Reverse transcriptase connection / Reverse transcriptase connection domain / Reverse transcriptase thumb / Reverse transcriptase thumb domain / Integrase Zinc binding domain / Zinc finger integrase-type profile. / Integrase-like, N-terminal / Integrase DNA binding domain / Integrase, C-terminal domain superfamily, retroviral / Integrase, N-terminal zinc-binding domain ...
Similarity search - Domain/homology

Biological species

Human immunodeficiency virus type 1 group M subtype B

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.85 Å

Authors

Chopra, A. / Ruiz, F.X. / Bauman, J.D. / Arnold, E.

Funding support

United States, 1items

Citation

Journal: J.Med.Chem. / Year: 2023
Title: Halo Library, a Tool for Rapid Identification of Ligand Binding Sites on Proteins Using Crystallographic Fragment Screening.
Authors: Chopra, A. / Bauman, J.D. / Ruiz, F.X. / Arnold, E.

History

Deposition	Aug 2, 2022	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	May 31, 2023	Provider: repository / Type: Initial release
Revision 1.1	Oct 25, 2023	Group: Data collection / Refinement description Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	8dxe.cif.gz	480.6 KB	Display	PDBx/mmCIF format
PDB format	pdb8dxe.ent.gz	346.6 KB	Display	PDB format
PDBx/mmJSON format	8dxe.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	8dxe_validation.pdf.gz	1 MB	Display	wwPDB validaton report
Full document	8dxe_full_validation.pdf.gz	1 MB	Display
Data in XML	8dxe_validation.xml.gz	42.7 KB	Display
Data in CIF	8dxe_validation.cif.gz	63.3 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/dx/8dxe ftp://data.pdbj.org/pub/pdb/validation_reports/dx/8dxe	HTTPS FTP

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Related structure data

Related structure data	8dx2C 8dx3C 8dx8C 8dxbC 8dxgC 8dxhC 8dxiC 8dxjC 8dxkC 8dxlC 8dxmC 4g1qS S: Starting model for refinement C: citing same article (ref.)
Similar structure data	Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

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Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#33 - Sep 2002 HIV Reverse Transcriptase similarity (1) #227 - Nov 2018 Telomerase similarity (1) #163 - Jul 2013 HIV Capsid similarity (1)

Deposited unit

A: Reverse transcriptase/ribonuclease H

B: p51 RT

hetero molecules

115 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author&software

Unit cell

Length a, b, c (Å)	162.226, 72.717, 109.555
Angle α, β, γ (deg.)	90.000, 100.508, 90.000
Int Tables number	5
Space group name H-M	C121
Space group name Hall	C2y
Symmetry operation	#1: x,y,z #2: -x,y,-z #3: x+1/2,y+1/2,z #4: -x+1/2,y+1/2,-z

Components on special symmetry positions

ID	Model	Components
1	1	A-1022- HOH

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Protein , 2 types, 2 molecules AB

#1: Protein	Reverse transcriptase/ribonuclease H / Exoribonuclease H / p66 RT Mass: 63989.238 Da / Num. of mol.: 1 / Mutation: K172A, K173A, C280S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus type 1 group M subtype B (isolate BH10) Strain: isolate BH10 / Gene: gag-pol / Production host: Escherichia coli (E. coli) References: UniProt: P03366, RNA-directed DNA polymerase, DNA-directed DNA polymerase, retroviral ribonuclease H, exoribonuclease H
#2: Protein	p51 RT Mass: 50039.488 Da / Num. of mol.: 1 / Mutation: C280S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus type 1 group M subtype B (isolate BH10) Strain: isolate BH10 / Gene: gag-pol / Production host: Escherichia coli (E. coli) / References: UniProt: P03366

#1: Protein

Reverse transcriptase/ribonuclease H / Exoribonuclease H / p66 RT

Mass: 63989.238 Da / Num. of mol.: 1 / Mutation: K172A, K173A, C280S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Human immunodeficiency virus type 1 group M subtype B (isolate BH10)
Strain: isolate BH10 / Gene: gag-pol / Production host:

Escherichia coli (E. coli)
References: UniProt: P03366, RNA-directed DNA polymerase, DNA-directed DNA polymerase, retroviral ribonuclease H, exoribonuclease H

#2: Protein

p51 RT

Mass: 50039.488 Da / Num. of mol.: 1 / Mutation: C280S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Human immunodeficiency virus type 1 group M subtype B (isolate BH10)
Strain: isolate BH10 / Gene: gag-pol / Production host:

Escherichia coli (E. coli) / References: UniProt: P03366

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Non-polymers , 7 types, 667 molecules

#3: Chemical	ChemComp-0IF / 2-amino-6-fluorobenzonitrile Mass: 136.126 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₇H₅FN₂ / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical	ChemComp-T27 / 4-{[4-({4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile / Rilpivirine Mass: 366.419 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂₂H₁₈N₆ / Comment: medication, inhibitor*YM
#5: Chemical	ChemComp-DMS / DIMETHYL SULFOXIDE Mass: 78.133 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C₂H₆OS / Comment: DMSO, precipitant*YM
#6: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₂H₆O₂
#7: Chemical	ChemComp-MG / MAGNESIUM ION Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#8: Chemical	ChemComp-SO4 / SULFATE ION Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO₄
#9: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 652 / Source method: isolated from a natural source / Formula: H₂O

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Details

Has ligand of interest	Y

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Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal	Density Matthews: 2.79 Å³/Da / Density % sol: 55.85 %
Crystal grow	Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 6.5 Details: 10-12% PEG 8000, 4% PEG 400, 100 mM imidazole pH 6.4-6.6, 15 mM MgSO4, 100 mM amm sulfate, 5 mM TCEP PH range: 6.4-6.6

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Data collection

Diffraction

Mean temperature: 100 K / Serial crystal experiment: N

Diffraction source

Source:

SYNCHROTRON / Site:

APS

/ Beamline: 23-ID-D / Wavelength: 1 Å

Detector

Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Apr 19, 2019

Radiation

Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray

Radiation wavelength

Wavelength: 1 Å / Relative weight: 1

Reflection

Resolution: 1.85→50 Å / Num. obs: 106434 / % possible obs: 99.7 % / Redundancy: 3.6 % / R_merge(I) obs: 0.075 / R_pim(I) all: 0.045 / R_rim(I) all: 0.087 / Χ²: 1.074 / Net I/σ(I): 10.1 / Num. measured all: 380131

Reflection shell

Diffraction-ID: 1

Resolution (Å)	Redundancy (%)	R_merge(I) obs	Num. unique obs	CC_1/2	R_pim(I) all	R_rim(I) all	Χ²	% possible all
1.85-1.88	3.6	0.594	5240	0.718	0.363	0.698	0.97	99.4
1.88-1.92	3.5	0.514	5302	0.686	0.316	0.605	1.125	99.3
1.92-1.95	3.5	0.406	5272	0.773	0.251	0.479	1.135	99.3
1.95-1.99	3.4	0.327	5244	0.866	0.208	0.389	1.088	99.4
1.99-2.04	3.6	0.279	5323	0.907	0.171	0.328	1.097	99.6
2.04-2.08	3.5	0.236	5294	0.926	0.146	0.279	1.214	99.6
2.08-2.14	3.5	0.193	5303	0.949	0.119	0.228	1.113	99.6
2.14-2.19	3.7	0.17	5305	0.964	0.102	0.199	1.088	99.7
2.19-2.26	3.6	0.156	5297	0.953	0.095	0.184	1.201	99.7
2.26-2.33	3.6	0.136	5316	0.972	0.083	0.16	1.068	99.8
2.33-2.41	3.4	0.12	5320	0.977	0.075	0.142	1.039	99.8
2.41-2.51	3.6	0.11	5294	0.98	0.067	0.129	1.045	99.6
2.51-2.63	3.5	0.099	5345	0.983	0.06	0.117	1.067	99.6
2.63-2.76	3.7	0.092	5282	0.984	0.055	0.108	1.149	99.7
2.76-2.94	3.7	0.084	5348	0.986	0.05	0.098	1.036	99.8
2.94-3.16	3.6	0.079	5369	0.985	0.048	0.092	1.006	99.8
3.16-3.48	3.6	0.072	5312	0.988	0.044	0.085	1.099	99.8
3.48-3.99	3.8	0.064	5383	0.991	0.038	0.074	0.976	99.9
3.99-5.02	3.6	0.06	5384	0.991	0.036	0.07	1.008	99.9
5.02-50	3.6	0.055	5501	0.976	0.033	0.065	0.985	99.7

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Processing

Software

Name	Version	Classification
HKL-2000		data scaling
PHENIX	dev_3051	refinement
PDB_EXTRACT	3.27	data extraction
HKL-2000		data reduction
PHENIX		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 4G1Q

4g1q

Resolution: 1.85→42.06 Å / SU ML: 0.2028 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 22.3923
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.2166	3768	1.88 %
R_work	0.1889	196748	-
obs	0.1895	106428	94.98 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL

Displacement parameters

B_iso mean: 45.57 Å²

Refinement step

Cycle: LAST / Resolution: 1.85→42.06 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	7949	0	89	654	8692

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.013	8306
X-RAY DIFFRACTION	f_angle_d	1.1509	11289
X-RAY DIFFRACTION	f_chiral_restr	0.0789	1219
X-RAY DIFFRACTION	f_plane_restr	0.0076	1427
X-RAY DIFFRACTION	f_dihedral_angle_d	17.4351	3148

LS refinement shell

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Refine-ID	% reflection obs (%)
1.85-1.87	0.2972	107	0.2961	5815	X-RAY DIFFRACTION	75.96
1.87-1.9	0.2608	137	0.2748	7250	X-RAY DIFFRACTION	93.96
1.9-1.92	0.287	137	0.2652	7168	X-RAY DIFFRACTION	93.47
1.92-1.95	0.2564	136	0.2463	7137	X-RAY DIFFRACTION	93.3
1.95-1.98	0.3058	143	0.2388	7138	X-RAY DIFFRACTION	93.17
1.98-2.01	0.2458	143	0.2289	7178	X-RAY DIFFRACTION	93.9
2.01-2.04	0.2547	137	0.2244	7251	X-RAY DIFFRACTION	94.86
2.04-2.08	0.2239	137	0.2238	7337	X-RAY DIFFRACTION	94.36
2.08-2.11	0.2321	139	0.2176	7273	X-RAY DIFFRACTION	94.42
2.11-2.16	0.2436	139	0.2115	7281	X-RAY DIFFRACTION	95.36
2.16-2.2	0.248	143	0.2038	7327	X-RAY DIFFRACTION	95.66
2.2-2.25	0.2541	135	0.2086	7221	X-RAY DIFFRACTION	95.25
2.25-2.3	0.2609	138	0.2043	7359	X-RAY DIFFRACTION	95.28
2.3-2.36	0.2353	144	0.2044	7242	X-RAY DIFFRACTION	94.23
2.36-2.42	0.2746	140	0.2054	7306	X-RAY DIFFRACTION	95.4
2.42-2.49	0.2579	141	0.2048	7400	X-RAY DIFFRACTION	96.2
2.49-2.57	0.2948	138	0.2087	7327	X-RAY DIFFRACTION	95.56
2.57-2.66	0.2479	144	0.2049	7428	X-RAY DIFFRACTION	96.53
2.66-2.77	0.2549	143	0.2002	7387	X-RAY DIFFRACTION	96.61
2.77-2.9	0.2229	145	0.1945	7426	X-RAY DIFFRACTION	97
2.9-3.05	0.2402	143	0.1954	7422	X-RAY DIFFRACTION	96.68
3.05-3.24	0.207	143	0.1902	7483	X-RAY DIFFRACTION	97.68
3.24-3.49	0.1903	142	0.1847	7496	X-RAY DIFFRACTION	97.59
3.49-3.84	0.1908	146	0.1693	7551	X-RAY DIFFRACTION	98.1
3.84-4.4	0.2006	142	0.154	7473	X-RAY DIFFRACTION	97.79
4.4-5.54	0.1937	146	0.163	7552	X-RAY DIFFRACTION	98.16
5.54-42.06	0.1579	140	0.1735	7520	X-RAY DIFFRACTION	98.04

Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

ID	L11 (°²)	L12 (°²)	L13 (°²)	L22 (°²)	L23 (°²)	L33 (°²)	S11 (Å °)	S12 (Å °)	S13 (Å °)	S21 (Å °)	S22 (Å °)	S23 (Å °)	S31 (Å °)	S32 (Å °)	S33 (Å °)	T11 (Å²)	T12 (Å²)	T13 (Å²)	T22 (Å²)	T23 (Å²)	T33 (Å²)	Origin x (Å)	Origin y (Å)	Origin z (Å)
1	0.129426999612	0.347439111714	0.0434685993728	0.10873903499	0.424647231588	1.07984301455	0.148438884106	-0.127750478929	-0.132022646778	0.158624758108	0.0415447737	0.0538562551076	0.188329776284	-0.0523894896088	0.0764435268811	0.366352519411	0.0160823034878	-0.00344159314028	0.245849590501	0.0591005646087	0.273868550366	43.8876043127	-21.3972429361	52.8371047804
2	0.898330810245	-0.439861421116	0.806478430115	0.106611220652	-0.32009668062	0.648469862943	0.0258980628912	-0.0897537645158	-0.12765403587	0.0384261268644	0.0864876740384	0.104014471188	0.0755811841202	-0.136730197487	0.000699661953934	0.177606347439	0.0049777160273	0.0345668408727	0.240579320914	0.00260026748133	0.255854107913	24.1357759221	-3.63358611766	11.778146231
3	0.575727404982	-0.00806982692968	0.290006054179	0.648871460948	-0.265505951965	0.438704625552	-0.0270170870497	0.0174708265724	-0.0183387677415	0.179330637438	-0.0734871553742	0.00303989184153	-0.0767837623537	0.141337659352	2.01827829979E-9	0.273336939033	-0.0271946448905	-0.00670560007039	0.280931506145	0.00187022328353	0.22081760294	56.1730966314	1.40877435201	36.7921327062
4	1.12576014997	-0.683820895627	0.879277903445	0.730641995455	-0.270523260546	0.404509273017	-0.31829710028	0.483598991156	0.430517649489	0.324371372704	0.124796008867	-0.479508052561	-0.0912642560281	0.564057027938	0.00895854038479	0.279335547361	-0.3007395861	-0.099523727562	0.413543056929	0.142772953751	0.399570890747	63.2595554548	15.3666743795	31.1754437004
5	0.357304720726	0.342348382021	0.283315477737	0.937205251406	0.0232312086307	0.986168072952	-0.172086837857	0.108388514761	0.221782206746	0.15774298684	0.0173146896994	0.0212706837351	-0.21806161553	0.0922827137668	-0.00218863365176	0.235713445864	-0.029481291305	0.0135974007347	0.221007037498	-0.00878449024351	0.226186076034	32.8656280102	24.809436095	7.73425081382
6	0.308017548415	-0.0254573579372	0.155012206989	0.516270856508	-0.0937583239438	0.284308283168	0.0141423589042	0.116963992681	0.0509968556688	0.0605949806884	-0.118681796534	0.0243560931039	-0.118299595984	0.0230510210759	-2.77142943325E-8	0.231244210329	-0.0135784089088	0.0165532745862	0.214298591446	-0.00555012456028	0.230540104703	42.9547454226	10.4159577211	19.9922870891

Refinement TLS group

Refine-ID: X-RAY DIFFRACTION

ID	Refine TLS-ID	Selection details	Auth asym-ID	Label asym-ID	Auth seq-ID	Label seq-ID
1	1	chain 'A' and (resid -1 through 296 )	A	A	-1 - 296	1 - 298
2	2	chain 'A' and (resid 297 through 554 )	A	A	297 - 554	299 - 556
3	3	chain 'B' and (resid 5 through 83 )	B	C	5 - 83	1 - 79
4	4	chain 'B' and (resid 84 through 238 )	B	C	84 - 238	80 - 225
5	5	chain 'B' and (resid 239 through 363 )	B	C	239 - 363	226 - 350
6	6	chain 'B' and (resid 364 through 428 )	B	C	364 - 428	351 - 415

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