PDB-8dxj: HIV-1 reverse transcriptase/rilpivirine with bound fragment 1-N-m...

ID or keywords:

Entry

Database: PDB / ID: 8dxj

Title

HIV-1 reverse transcriptase/rilpivirine with bound fragment 1-N-methyl-4-(trifluoromethyl)benzene-1,2-diamine 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: 1.8 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	8dxj.cif.gz	479.3 KB	Display	PDBx/mmCIF format
PDB format	pdb8dxj.ent.gz	345 KB	Display	PDB format
PDBx/mmJSON format	8dxj.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	8dxj_validation.pdf.gz	1 MB	Display	wwPDB validaton report
Full document	8dxj_full_validation.pdf.gz	1 MB	Display
Data in XML	8dxj_validation.xml.gz	41.5 KB	Display
Data in CIF	8dxj_validation.cif.gz	60.5 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/dx/8dxj ftp://data.pdbj.org/pub/pdb/validation_reports/dx/8dxj	HTTPS FTP

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Related structure data

Related structure data	8dx2C 8dx3C 8dx8C 8dxbC 8dxeC 8dxgC 8dxhC 8dxiC 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)	162.243, 72.809, 109.454
Angle α, β, γ (deg.)	90.000, 100.513, 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, 576 molecules

#3: 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
#4: Chemical	ChemComp-DMS / DIMETHYL SULFOXIDE Mass: 78.133 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C₂H₆OS / Comment: DMSO, precipitant*YM
#5: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₂H₆O₂
#6: Chemical	ChemComp-MG / MAGNESIUM ION Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#7: Chemical	ChemComp-U43 / N~1~-methyl-4-(trifluoromethyl)benzene-1,2-diamine Mass: 190.166 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₈H₉F₃N₂ / Feature type: SUBJECT OF INVESTIGATION
#8: Chemical	ChemComp-SO4 / SULFATE ION Mass: 96.063 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: SO₄
#9: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 560 / 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: 2.83 Å³/Da / Density % sol: 56.48 %
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: 1.8→50 Å / Num. obs: 113731 / % possible obs: 97.8 % / Redundancy: 3.2 % / R_merge(I) obs: 0.063 / R_pim(I) all: 0.039 / R_rim(I) all: 0.074 / Χ²: 1.061 / Net I/σ(I): 11.6 / Num. measured all: 363064

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
1.8-1.83	2.5	0.497	5445	0.45	0.361	0.618	0.914	94
1.83-1.86	2.7	0.445	5471	0.611	0.309	0.545	0.96	94.5
1.86-1.9	2.8	0.377	5514	0.709	0.261	0.461	1.025	95.1
1.9-1.94	2.8	0.319	5515	0.781	0.219	0.389	1.081	95.6
1.94-1.98	2.8	0.277	5560	0.837	0.191	0.339	1.155	96
1.98-2.03	2.9	0.242	5596	0.881	0.163	0.294	1.148	96.8
2.03-2.08	3	0.205	5622	0.91	0.135	0.247	1.192	97.3
2.08-2.13	3	0.176	5650	0.934	0.117	0.213	1.212	97.9
2.13-2.2	3.2	0.16	5680	0.952	0.102	0.19	1.196	98.1
2.2-2.27	3.2	0.141	5729	0.958	0.09	0.168	1.156	98.2
2.27-2.35	3.2	0.127	5717	0.965	0.082	0.152	1.054	98.5
2.35-2.44	3.2	0.116	5643	0.968	0.074	0.138	0.968	98.6
2.44-2.55	3.3	0.105	5759	0.974	0.067	0.125	0.987	98.9
2.55-2.69	3.5	0.094	5791	0.978	0.058	0.111	1.033	99.1
2.69-2.86	3.6	0.083	5740	0.987	0.05	0.097	1.059	99.3
2.86-3.08	3.4	0.074	5812	0.988	0.046	0.087	1.017	99.6
3.08-3.39	3.6	0.066	5828	0.991	0.04	0.077	1.061	99.7
3.39-3.88	3.8	0.058	5834	0.993	0.035	0.068	0.984	99.7
3.88-4.88	3.6	0.053	5847	0.993	0.032	0.062	0.993	99.9
4.88-50	3.6	0.044	5978	0.995	0.026	0.051	1.06	99.7

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Processing

Software

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

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 4g1q

4g1q

Resolution: 1.8→42.94 Å / SU ML: 0.21 / Cross valid method: FREE R-VALUE / σ(F): 1.39 / Phase error: 22.4748
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2

	R_factor	Num. reflection	% reflection
R_free	0.2071	3653	1.77 %
R_work	0.1871	202554	-
obs	0.1874	113726	90.04 %

Solvent computation

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

Displacement parameters

B_iso mean: 49.05 Å²

Refinement step

Cycle: LAST / Resolution: 1.8→42.94 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	7949	0	98	560	8607

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.0053	8303
X-RAY DIFFRACTION	f_angle_d	0.8092	11286
X-RAY DIFFRACTION	f_chiral_restr	0.0545	1217
X-RAY DIFFRACTION	f_plane_restr	0.0044	1426
X-RAY DIFFRACTION	f_dihedral_angle_d	16.564	3145

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 (%)
1.8-1.82	0.3108	113	0.3123	6154	X-RAY DIFFRACTION	70.96
1.82-1.85	0.2849	124	0.302	7042	X-RAY DIFFRACTION	81.56
1.85-1.87	0.2931	125	0.2866	7129	X-RAY DIFFRACTION	82.17
1.87-1.9	0.3039	130	0.2682	7196	X-RAY DIFFRACTION	83.21
1.9-1.93	0.285	131	0.2575	7278	X-RAY DIFFRACTION	83.75
1.93-1.96	0.2439	133	0.2492	7316	X-RAY DIFFRACTION	84.87
1.96-2	0.2599	134	0.242	7239	X-RAY DIFFRACTION	84.27
2-2.03	0.248	134	0.2294	7599	X-RAY DIFFRACTION	87.3
2.03-2.07	0.2764	144	0.2271	7589	X-RAY DIFFRACTION	87.73
2.07-2.11	0.2592	130	0.2192	7548	X-RAY DIFFRACTION	87.02
2.11-2.16	0.254	139	0.202	7848	X-RAY DIFFRACTION	90.68
2.16-2.21	0.2215	143	0.2053	7847	X-RAY DIFFRACTION	91.06
2.21-2.27	0.2161	141	0.1957	7975	X-RAY DIFFRACTION	91.68
2.27-2.33	0.2128	139	0.197	7879	X-RAY DIFFRACTION	91.79
2.33-2.4	0.2135	146	0.193	7876	X-RAY DIFFRACTION	90.51
2.4-2.47	0.2337	147	0.1975	8073	X-RAY DIFFRACTION	93.08
2.47-2.56	0.2419	144	0.1979	7921	X-RAY DIFFRACTION	92.2
2.56-2.66	0.2111	149	0.199	8159	X-RAY DIFFRACTION	94.01
2.66-2.78	0.2617	139	0.1957	8240	X-RAY DIFFRACTION	95.24
2.78-2.93	0.2107	149	0.1926	8315	X-RAY DIFFRACTION	96.21
2.93-3.11	0.2552	149	0.2016	8265	X-RAY DIFFRACTION	95.54
3.11-3.36	0.2342	155	0.1875	8293	X-RAY DIFFRACTION	96.39
3.36-3.69	0.1661	153	0.1751	8475	X-RAY DIFFRACTION	97.39
3.69-4.23	0.1735	156	0.1554	8520	X-RAY DIFFRACTION	98.07
4.23-5.32	0.1652	153	0.155	8337	X-RAY DIFFRACTION	96.84
5.32-42.94	0.178	153	0.171	8441	X-RAY DIFFRACTION	97.44

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	0.258812434572	0.107131564648	-0.160109668208	-0.0130532046942	0.243312337551	1.06739811014	0.0889339143153	-0.127756234351	-0.0948198380702	0.101605440502	0.0151163385396	0.0904205218861	0.164142946577	-0.0183285724357	0.00217087995067	0.396410808653	0.00925581108323	0.0388137400861	0.306978432597	0.036209635668	0.251968954946	45.3414940187	-17.2997034497	64.3737431477
2	0.41691744029	0.135178941317	0.560453627347	0.802686562402	0.230025085666	0.890726970111	0.304492808211	-0.262859962002	-0.374243039146	0.230661243297	0.0388860885733	0.0633708493382	0.221869116521	-0.149709892659	0.0219247811378	0.359884507992	-0.0269243110222	-0.0207134881801	0.319317646656	0.0754401089896	0.369096634101	42.0328664287	-25.9777986673	40.0376318436
3	0.857712720454	-0.486875544286	0.603863390376	0.368511145886	-0.26447421318	0.377063705933	0.00215156554434	-0.0944909272325	-0.131144055437	0.064528329105	0.0965484776838	0.122919199957	0.0454783683821	-0.127745179727	3.09138143566E-9	0.217963765393	0.0045856937838	0.0251076169455	0.273005398977	0.00182317852536	0.278216732828	24.1957762072	-3.63903204431	11.8413297168
4	0.698949400137	-0.219989599139	0.597248487132	0.821295933326	-0.282209977689	0.622907301592	-0.061279591509	0.0277480144124	0.0716443334935	0.168918327831	-0.0409636837098	0.00199456346026	-0.108767835116	0.163231722803	-3.81674001484E-9	0.306860683149	-0.0359645205301	-0.00469280761491	0.312765305482	0.0118791635694	0.265230094736	56.2724646733	1.37231476825	36.7195201207
5	0.124396725	-0.122993788803	0.0245589908014	0.198195690312	0.0318505206151	0.0850475359282	-0.425563056191	0.269295714199	0.583981766152	0.195624156087	0.0638355251727	0.0159096183228	0.00626963506049	0.0413456784657	-0.0212924531455	0.597119517074	-0.104074061599	-0.151498299196	0.323382905813	0.100071949336	0.727529564227	55.7798790687	26.2105337936	33.7512828461
6	1.29756595663	-0.474080628472	0.966448603454	1.01219094328	-0.207973358176	0.506523073118	-0.23363266527	0.410645778446	0.382432579173	0.163815001517	-0.0197954638696	-0.513598734818	-0.0970757764103	0.525950611412	-0.00335425707652	0.346743193931	-0.222334694948	-0.0623958039776	0.436822758673	0.116688485107	0.406733962212	64.5550768137	13.6698199214	30.6972364336
7	0.343668202256	0.23315963204	0.521547926061	1.08626044901	-0.148611672678	1.19172604066	-0.162910238372	0.144352282293	0.164349400521	0.136119576887	0.0217147736499	-0.0297021032716	-0.173322787931	0.121278604552	8.23447662924E-9	0.258923789388	-0.0323657145054	0.0135870235281	0.276443337607	-0.0106331890306	0.256334827073	32.7932245889	25.0217419498	7.75207829136
8	0.45819542983	-0.0236784758319	0.136231088359	0.631590606394	-0.199917224605	0.43685109421	0.00719061017443	0.0978706846917	0.0898602262099	0.0297225205875	-0.115957143788	0.0122952462253	-0.0762404740431	0.0113866951907	3.45721814127E-8	0.268976892622	-0.0222737223172	0.00379595278548	0.242680041083	-0.00131458499468	0.269198435599	43.1928571312	10.0401904295	20.2207508886

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 155 )	A	A	-1 - 155	1 - 157
2	2	chain 'A' and (resid 156 through 296 )	A	A	156 - 296	158 - 298
3	3	chain 'A' and (resid 297 through 554 )	A	A	297 - 554	299 - 556
4	4	chain 'B' and (resid 5 through 83 )	B	B	5 - 83	1 - 79
5	5	chain 'B' and (resid 84 through 104 )	B	B	84 - 104	80 - 100
6	6	chain 'B' and (resid 105 through 238 )	B	B	105 - 238	101 - 225
7	7	chain 'B' and (resid 239 through 363 )	B	B	239 - 363	226 - 350
8	8	chain 'B' and (resid 364 through 428 )	B	B	364 - 428	351 - 415

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-Feb 9, 2022. New format data for meta-information of EMDB entries

-Aug 12, 2020. Covid-19 info

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Non-polymers , 7 types, 576 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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Yorodumi