PDB-8dx8: HIV-1 reverse transcriptase/rilpivirine with bound fragment 2-chl...

ID or keywords:

Entry

Database: PDB / ID: 8dx8

Title

HIV-1 reverse transcriptase/rilpivirine with bound fragment 2-chloro-6-fluorophenethylamine at the 415 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	8dx8.cif.gz	482.6 KB	Display	PDBx/mmCIF format
PDB format	pdb8dx8.ent.gz	348.3 KB	Display	PDB format
PDBx/mmJSON format	8dx8.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	8dx8_validation.pdf.gz	1.2 MB	Display	wwPDB validaton report
Full document	8dx8_full_validation.pdf.gz	1.2 MB	Display
Data in XML	8dx8_validation.xml.gz	43.7 KB	Display
Data in CIF	8dx8_validation.cif.gz	63.2 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/dx/8dx8 ftp://data.pdbj.org/pub/pdb/validation_reports/dx/8dx8	HTTPS FTP

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Related structure data

Related structure data	8dx2C 8dx3C 8dxbC 8dxeC 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

116 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)	161.672, 73.124, 109.347
Angle α, β, γ (deg.)	90.000, 99.905, 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

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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, 601 molecules

#3: Chemical	ChemComp-W15 / 2-(2-chloro-6-fluorophenyl)ethan-1-amine Mass: 173.615 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₈H₉ClFN / 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.: 5 / Source method: obtained synthetically / Formula: SO₄
#9: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 583 / 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: 55.94 %
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 S 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: 105168 / % possible obs: 98.7 % / Redundancy: 3.2 % / R_merge(I) obs: 0.066 / R_pim(I) all: 0.041 / R_rim(I) all: 0.078 / Χ²: 1.086 / Net I/σ(I): 10.6 / Num. measured all: 333839

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	2.5	0.541	5145	0.446	0.397	0.675	0.899	96.2
1.88-1.92	2.6	0.514	5109	0.417	0.368	0.636	0.933	96.8
1.92-1.95	2.7	0.431	5079	0.631	0.302	0.53	0.971	96.8
1.95-1.99	2.6	0.379	5123	0.704	0.269	0.467	1.011	96.9
1.99-2.04	2.8	0.343	5239	0.762	0.233	0.417	1.074	98.1
2.04-2.08	2.9	0.287	5171	0.849	0.195	0.349	1.174	98
2.08-2.14	2.9	0.243	5210	0.893	0.163	0.294	1.162	98.3
2.14-2.19	3.1	0.215	5277	0.922	0.139	0.257	1.166	98.9
2.19-2.26	3.2	0.193	5235	0.924	0.124	0.23	1.18	98.7
2.26-2.33	3.2	0.172	5247	0.943	0.111	0.206	1.216	98.6
2.33-2.41	3.1	0.147	5239	0.959	0.096	0.176	1.117	99.1
2.41-2.51	3.3	0.136	5288	0.964	0.085	0.161	1.016	99.2
2.51-2.63	3.3	0.116	5305	0.972	0.074	0.139	0.914	99.4
2.63-2.76	3.5	0.104	5293	0.979	0.064	0.123	1.16	99.7
2.76-2.94	3.5	0.09	5325	0.984	0.054	0.105	1.098	99.6
2.94-3.16	3.5	0.077	5339	0.987	0.047	0.091	1.01	99.8
3.16-3.48	3.6	0.065	5321	0.991	0.04	0.077	1.033	99.8
3.48-3.99	3.8	0.054	5356	0.994	0.032	0.063	1.158	100
3.99-5.02	3.6	0.048	5377	0.995	0.029	0.056	1.026	99.9
5.02-50	3.7	0.042	5490	0.996	0.025	0.049	1.243	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→41.96 Å / SU ML: 0.2367 / Cross valid method: FREE R-VALUE / σ(F): 1.37 / Phase error: 23.9422
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.2231	3643	1.91 %
R_work	0.2007	186980	-
obs	0.2011	105163	91.01 %

Solvent computation

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

Displacement parameters

B_iso mean: 52.15 Å²

Refinement step

Cycle: LAST / Resolution: 1.85→41.96 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	7947	0	105	583	8635

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.0058	8337
X-RAY DIFFRACTION	f_angle_d	0.9609	11334
X-RAY DIFFRACTION	f_chiral_restr	0.0577	1220
X-RAY DIFFRACTION	f_plane_restr	0.0062	1431
X-RAY DIFFRACTION	f_dihedral_angle_d	19.0164	3159

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 (%)
1.85-1.88	0.3343	127	0.3491	6089	X-RAY DIFFRACTION	76.8
1.88-1.9	0.3773	121	0.3274	6456	X-RAY DIFFRACTION	82.37
1.9-1.93	0.3222	129	0.3049	6639	X-RAY DIFFRACTION	83.36
1.93-1.96	0.314	124	0.2929	6494	X-RAY DIFFRACTION	82.93
1.96-1.99	0.2648	126	0.2775	6533	X-RAY DIFFRACTION	81.76
1.99-2.02	0.3075	134	0.2673	6750	X-RAY DIFFRACTION	85.23
2.02-2.06	0.2496	135	0.259	6890	X-RAY DIFFRACTION	87.62
2.06-2.1	0.2695	134	0.2465	6910	X-RAY DIFFRACTION	87.16
2.1-2.14	0.2677	137	0.237	6996	X-RAY DIFFRACTION	89.68
2.14-2.18	0.2853	143	0.2284	7172	X-RAY DIFFRACTION	90.99
2.18-2.23	0.2777	144	0.2204	7313	X-RAY DIFFRACTION	91.49
2.23-2.28	0.2472	138	0.2207	7245	X-RAY DIFFRACTION	91.46
2.28-2.34	0.2359	135	0.215	7124	X-RAY DIFFRACTION	90.5
2.34-2.4	0.2534	136	0.2181	7046	X-RAY DIFFRACTION	88.67
2.4-2.47	0.1995	144	0.2125	7328	X-RAY DIFFRACTION	93.44
2.47-2.55	0.2321	142	0.2119	7412	X-RAY DIFFRACTION	93.79
2.55-2.64	0.2353	149	0.2084	7503	X-RAY DIFFRACTION	95.32
2.64-2.75	0.2219	146	0.211	7615	X-RAY DIFFRACTION	96.4
2.75-2.87	0.2565	153	0.2093	7648	X-RAY DIFFRACTION	96.63
2.87-3.02	0.2174	143	0.2032	7462	X-RAY DIFFRACTION	94.41
3.02-3.21	0.2572	144	0.2021	7579	X-RAY DIFFRACTION	95.78
3.21-3.46	0.223	151	0.1914	7687	X-RAY DIFFRACTION	97.21
3.46-3.81	0.1873	146	0.1739	7800	X-RAY DIFFRACTION	98.86
3.81-4.36	0.1813	156	0.1648	7736	X-RAY DIFFRACTION	97.66
4.36-5.49	0.1983	150	0.1676	7755	X-RAY DIFFRACTION	98.28
5.49-41.96	0.1984	156	0.1916	7798	X-RAY DIFFRACTION	98.48

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	0.540967334053	-0.0299647365292	-0.197463685773	0.764252886666	0.573120894552	1.0724727804	0.0376612455134	-0.179550304138	-0.122657341965	0.134069871259	0.0669106731957	0.124391090177	0.0754845782998	0.0795536363983	0.0302753288794	0.316502156659	0.0585443715751	0.0364792392732	0.263051185478	0.04779675495	0.203907380276	48.316661182	-18.3445701055	60.5252652173
2	0.746334814042	0.875288115193	0.322316969389	1.03735730923	0.187904999183	1.10298846493	0.314555016493	-0.302031904035	-0.39116972949	0.251461711408	0.0465153627574	0.160620727506	0.214779813487	-0.27682684768	0.203171002107	0.320963913203	-0.0156868764252	0.034171484164	0.257700830308	0.0515977567358	0.253459831886	36.7959204666	-26.9112577184	38.3728910326
3	0.718669380824	-0.738704923432	0.72582840575	0.715048683185	-0.661590650024	0.297508310106	0.0296856195503	-0.0601855794623	-0.11853146426	0.00448391007998	0.075509014593	0.118794187222	0.104380879852	-0.153640505804	-5.63322663408E-5	0.168094334416	0.0140442614419	0.0114961645142	0.232359886943	-0.0110790421146	0.229660021607	28.6439458818	-8.91345942138	14.1077263151
4	0.668139490679	-0.236753765687	-0.0753488145037	0.258013847058	-0.224493267174	0.59250547733	-0.00959926181723	-0.229291513726	-0.208206436798	0.0579114843219	0.127330242785	0.0499839451684	-0.0313071338397	-0.0862148031689	0.0655704228337	0.143328831223	0.0151605049481	0.0347037172751	0.324315623735	0.0190870712275	0.305570602973	14.0791651569	8.67587993454	6.82941459878
5	0.69704419404	-0.113585887316	0.455073404671	0.656893320409	-0.556065927405	0.622436164822	-0.0977627172312	-0.0216810977888	0.0619844880062	0.225059114664	-0.0444406814909	0.0330113613032	-0.181088185955	0.262008741661	-0.00233892864318	0.311516254601	-0.0557125068741	-0.0275088137167	0.284320764425	0.000182320550845	0.254276933996	56.6251013624	1.4004469608	36.5661665743
6	1.39460756012	-0.895610028791	0.819052714433	1.13615229353	-0.128817619816	0.557452217226	-0.257420429148	0.577015431663	0.594298224564	0.402755367144	-0.0137352665487	-0.542293085066	-0.154272265695	0.714140788782	-0.283971302792	0.262666209198	-0.351895101913	-0.15459336225	0.485246266654	0.220714857933	0.480344413793	63.6307136376	15.5715591956	30.9092556884
7	0.228446979321	0.346909020889	0.188657710356	1.24696625086	0.105490040883	0.474109707147	-0.0787632427018	-0.0885457238198	0.231558164784	0.167214941323	0.0122037108723	0.214428131661	-0.30062103022	-0.149086496918	0.0118095647806	0.303132412339	-0.0339398049661	0.0254274863127	0.291801875803	-0.0273294965058	0.300581176276	28.5620882331	29.2979867886	5.28650073635
8	0.325045961231	-0.298199530499	0.0129437468518	1.38585504299	-0.286849283109	0.388920001273	0.0613264392013	0.11506380057	0.0696361060678	0.0308455429028	-0.264033114289	-0.000331916629755	-0.1315469962	0.0702601588831	-0.00379817830568	0.286699010603	-0.0193288404853	-0.00541331542772	0.237143703744	-0.00740610302285	0.244976432057	42.7306136264	12.4413681392	17.9473700916

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 194 )	A	A	-1 - 194	1 - 196
2	2	chain 'A' and (resid 195 through 296 )	A	A	195 - 296	197 - 298
3	3	chain 'A' and (resid 297 through 473 )	A	A	297 - 473	299 - 475
4	4	chain 'A' and (resid 474 through 554 )	A	A	474 - 554	476 - 556
5	5	chain 'B' and (resid 5 through 83 )	B	C	5 - 83	1 - 79
6	6	chain 'B' and (resid 84 through 238 )	B	C	84 - 238	80 - 225
7	7	chain 'B' and (resid 239 through 325 )	B	C	239 - 325	226 - 312
8	8	chain 'B' and (resid 326 through 428 )	B	C	326 - 428	313 - 415

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Protein , 2 types, 2 molecules AB

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Non-polymers , 7 types, 601 molecules

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Details

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Experimental details

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Experiment

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Sample preparation

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Data collection

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Processing

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