PDB-6cgf: Crystal structure of HIV-1 Y188L mutant reverse transcriptase in ...

ID or keywords:

Entry

Database: PDB / ID: 6cgf

Title

Crystal structure of HIV-1 Y188L mutant reverse transcriptase in complex with non-nucleoside inhibitor K-5a2

Components

Reverse transcriptase/ribonuclease H
p51 RT

Keywords

REPLICATION / non-nucleoside inhibitor

Function / homology

Function and homology information

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

HIV Type 1 Reverse Transcriptase, subunit A, domain 1 / HIV Type 1 Reverse Transcriptase; Chain A, domain 1 / Reverse transcriptase/Diguanylate cyclase domain / Ribonuclease H-like superfamily/Ribonuclease H / Reverse transcriptase connection / Reverse transcriptase connection domain / Reverse transcriptase thumb / Reverse transcriptase thumb domain / Integrase Zinc binding domain / Zinc finger integrase-type profile. ...
Similarity search - Domain/homology

Biological species

Human immunodeficiency virus type 1 group M subtype B

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.94 Å

Authors

Yang, Y. / Nguyen, L.A. / Smithline, Z.B. / Steitz, T.A.

Funding support

United States, 1items

Citation

Journal: Elife / Year: 2018
Title: Structural basis for potent and broad inhibition of HIV-1 RT by thiophene[3,2-d]pyrimidine non-nucleoside inhibitors.
Authors: Yang, Y. / Kang, D. / Nguyen, L.A. / Smithline, Z.B. / Pannecouque, C. / Zhan, P. / Liu, X. / Steitz, T.A.

History

Deposition	Feb 20, 2018	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Aug 1, 2018	Provider: repository / Type: Initial release
Revision 1.1	Nov 20, 2019	Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.2	Oct 4, 2023	Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr2_auth_seq_id

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	6cgf.cif.gz	446.7 KB	Display	PDBx/mmCIF format
PDB format	pdb6cgf.ent.gz	365.1 KB	Display	PDB format
PDBx/mmJSON format	6cgf.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	6cgf_validation.pdf.gz	826 KB	Display	wwPDB validaton report
Full document	6cgf_full_validation.pdf.gz	868.3 KB	Display
Data in XML	6cgf_validation.xml.gz	48.6 KB	Display
Data in CIF	6cgf_validation.cif.gz	70.4 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/cg/6cgf ftp://data.pdbj.org/pub/pdb/validation_reports/cg/6cgf	HTTPS FTP

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Related structure data

Related structure data	6c0jC 6c0kC 6c0lC 6c0nC 6c0oC 6c0pC 6c0rC 6dufC 6dugC 6duhC 4g1qS S: Starting model for refinement C: citing same article (ref.)
Similar structure data	6x4c-d 6eli-d 4kfb-d 5vqr-d 3bgr-d 6c0p-d 2zd1-d 4i2p-d 5vqu-d 4g1q-d 5vqv-d Search similar-shape structures by Omokage search (details) 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

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

1

Idetical with deposited unit
defined by author&software
Evidence: gel filtration

Unit cell

Length a, b, c (Å)	162.700, 72.704, 109.048
Angle α, β, γ (deg.)	90.00, 100.21, 90.00
Int Tables number	5
Space group name H-M	C121

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Protein , 2 types, 2 molecules AB

#1: Protein	Reverse transcriptase/ribonuclease H / Exoribonuclease H / p66 RT Mass: 63939.223 Da / Num. of mol.: 1 / Fragment: p66 subunit, residues 600-1154 / Mutation: K172A, K173A, Y188L, C280S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus type 1 group M subtype B Gene: gag-pol / Production host: Escherichia coli BL21(DE3) (bacteria) 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 / Fragment: p51 subunit, residues 600-1027 / Mutation: C280S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus type 1 group M subtype B Gene: gag-pol / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P03366, RNA-directed DNA polymerase

#1: Protein

Reverse transcriptase/ribonuclease H / Exoribonuclease H / p66 RT

Mass: 63939.223 Da / Num. of mol.: 1 / Fragment: p66 subunit, residues 600-1154 / Mutation: K172A, K173A, Y188L, C280S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Human immunodeficiency virus type 1 group M subtype B
Gene: gag-pol / Production host:

Escherichia coli BL21(DE3) (bacteria)
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 / Fragment: p51 subunit, residues 600-1027 / Mutation: C280S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.)

Human immunodeficiency virus type 1 group M subtype B
Gene: gag-pol / Production host:

Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P03366, RNA-directed DNA polymerase

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Non-polymers , 6 types, 752 molecules

#3: Chemical	ChemComp-K5A / 4-[(4-{[4-(4-cyano-2,6-dimethylphenoxy)thieno[3,2-d]pyrimidin-2-yl]amino}piperidin-1-yl)methyl]benzene-1-sulfonamide Mass: 548.680 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂₇H₂₈N₆O₃S₂ / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical	ChemComp-MG / MAGNESIUM ION Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#5: Chemical	ChemComp-NA / SODIUM ION Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#6: Chemical	ChemComp-SO4 / SULFATE ION Mass: 96.063 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: SO₄
#7: Chemical	... ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 23 / Source method: obtained synthetically / Formula: C₂H₆O₂
#8: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 719 / Source method: isolated from a natural source / Formula: H₂O

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 2.78 Å³/Da / Density % sol: 56 %
Crystal grow	Temperature: 277.15 K / Method: vapor diffusion, sitting drop Details: 50 mM MES buffer (pH 6.0-6.6), 10% (v/v) polyethylene glycol (PEG) 8000, 100 mM ammonium sulfate, 15 mM magnesium sulfate, and 10 mM spermine PH range: 6.0 - 6.6

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Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.97918 Å
Detector	Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 20, 2017
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97918 Å / Relative weight: 1
Reflection	Resolution: 1.94→42.065 Å / Num. obs: 92404 / % possible obs: 99.48 % / Redundancy: 3.4 % / B_iso Wilson estimate: 54 Å² / CC_1/2: 0.999 / R_merge(I) obs: 0.03208 / R_pim(I) all: 0.0203 / R_rim(I) all: 0.03806 / Net I/σ(I): 16.24
Reflection shell	Resolution: 1.94→2.06 Å / Redundancy: 3.2 % / R_merge(I) obs: 1 / Num. unique obs: 14861 / CC_1/2: 0.479 / R_rim(I) all: 1.197 / % possible all: 99.7

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Processing

Software

Name	Version	Classification
PHENIX	(1.13_2998)	refinement
XDS		data reduction
XDS		data scaling
PHENIX	(1.13_2998)	phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 4G1Q

4g1q

Resolution: 1.94→42.065 Å / SU ML: 0.29 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 25.64 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.2323	4621	5 %	Random selection
R_work	0.1936	-	-	-
obs	0.1955	92348	99.49 %	-

Solvent computation

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

Refinement step

Cycle: LAST / Resolution: 1.94→42.065 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	7934	0	167	719	8820

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.01	8426
X-RAY DIFFRACTION	f_angle_d	0.711	11433
X-RAY DIFFRACTION	f_dihedral_angle_d	14.815	5033
X-RAY DIFFRACTION	f_chiral_restr	0.065	1221
X-RAY DIFFRACTION	f_plane_restr	0.005	1432

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 (%)
1.9403-1.9623	0.398	151	0.394	2817	X-RAY DIFFRACTION	97
1.9623-1.9854	0.3618	154	0.3509	2932	X-RAY DIFFRACTION	100
1.9854-2.0096	0.3467	152	0.3274	2878	X-RAY DIFFRACTION	100
2.0096-2.0351	0.3416	156	0.3114	2976	X-RAY DIFFRACTION	100
2.0351-2.0618	0.3531	153	0.2878	2903	X-RAY DIFFRACTION	100
2.0618-2.0901	0.3174	154	0.2716	2917	X-RAY DIFFRACTION	100
2.0901-2.1199	0.2684	154	0.2573	2933	X-RAY DIFFRACTION	100
2.1199-2.1516	0.2651	153	0.2478	2911	X-RAY DIFFRACTION	100
2.1516-2.1852	0.2573	154	0.2397	2908	X-RAY DIFFRACTION	100
2.1852-2.221	0.2899	155	0.2341	2952	X-RAY DIFFRACTION	100
2.221-2.2593	0.302	153	0.2423	2904	X-RAY DIFFRACTION	100
2.2593-2.3004	0.3133	155	0.2445	2942	X-RAY DIFFRACTION	100
2.3004-2.3446	0.2235	154	0.2364	2931	X-RAY DIFFRACTION	100
2.3446-2.3925	0.2903	153	0.2355	2911	X-RAY DIFFRACTION	100
2.3925-2.4445	0.2583	153	0.23	2896	X-RAY DIFFRACTION	100
2.4445-2.5014	0.2428	153	0.22	2913	X-RAY DIFFRACTION	100
2.5014-2.5639	0.2702	155	0.2145	2948	X-RAY DIFFRACTION	100
2.5639-2.6332	0.2368	154	0.2071	2923	X-RAY DIFFRACTION	100
2.6332-2.7107	0.2294	155	0.2097	2942	X-RAY DIFFRACTION	100
2.7107-2.7982	0.2513	155	0.2093	2945	X-RAY DIFFRACTION	99
2.7982-2.8982	0.2307	152	0.2092	2899	X-RAY DIFFRACTION	100
2.8982-3.0142	0.242	154	0.2052	2910	X-RAY DIFFRACTION	99
3.0142-3.1513	0.2567	153	0.2012	2916	X-RAY DIFFRACTION	99
3.1513-3.3174	0.2174	153	0.1928	2904	X-RAY DIFFRACTION	98
3.3174-3.5251	0.2518	153	0.19	2914	X-RAY DIFFRACTION	99
3.5251-3.7971	0.2205	154	0.1795	2929	X-RAY DIFFRACTION	99
3.7971-4.179	0.1842	155	0.1592	2939	X-RAY DIFFRACTION	99
4.179-4.7829	0.2076	156	0.1591	2967	X-RAY DIFFRACTION	100
4.7829-6.0232	0.2412	157	0.1831	2967	X-RAY DIFFRACTION	99
6.0232-42.0748	0.2117	158	0.1867	3000	X-RAY DIFFRACTION	98

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	0.2926	0.7942	-0.2583	0.5771	0.3691	3.0472	0.2333	-0.2563	-0.1724	0.3296	0.0401	0.3066	0.1232	-0.25	-0.2396	0.8393	0.0395	0.0153	0.6273	0.1875	0.6969	44.4478	-20.5236	52.6898
2	3.8902	-1.294	1.9502	0.8548	-0.5405	1.5824	0.1033	-0.3336	-0.6366	0.066	0.2375	0.3075	0.2002	-0.3513	-0.2455	0.3589	-0.0534	0.0401	0.4038	0.0288	0.5	24.5529	-3.3782	11.9503
3	5.4099	-0.4319	1.4209	5.5085	-0.5845	3.6355	0.0281	-0.0212	0.1681	0.4831	-0.1426	-0.1859	-0.2897	0.3644	0.0499	0.5294	-0.0498	-0.0137	0.4705	0.0644	0.3236	56.5653	2.4034	36.5691
4	1.4723	2.0439	-1.4328	5.6201	-5.4146	5.757	-0.1207	-0.1046	1.1218	0.8149	-0.1223	0.5622	-1.2938	0.7349	0.3083	1.2668	-0.2485	-0.1378	0.7744	0.0112	1.1357	55.8313	27.0881	33.3178
5	2.4234	-0.032	0.8157	4.1198	-0.9403	2.5613	-0.2391	0.3826	0.3995	0.1814	-0.0284	-0.8478	-0.4092	1.0342	0.1425	0.7453	-0.3022	-0.1094	0.8127	0.08	0.6187	64.2362	14.9526	30.4057
6	0.2972	0.244	0.0142	2.363	-0.6844	2.1634	-0.1721	0.1329	0.4188	0.1986	-0.1717	-0.1918	0.2184	0.4231	0.3455	0.4415	-0.0235	-0.003	0.5663	0.0449	0.5147	30.7846	25.7059	2.4153
7	3.314	-0.0203	2.61	2.7604	-0.2338	4.4214	-0.5275	0.1713	0.6889	0.3869	0.023	-0.0718	-0.8033	0.0862	0.4711	0.4945	-0.0855	0.0354	0.3799	0.01	0.4377	33.1163	25.3626	8.923
8	3.8755	-0.1291	1.6077	3.2075	-0.3495	2.6387	-0.0434	0.144	0.324	0.2396	-0.1057	-0.0244	-0.3592	0.1124	0.157	0.5057	-0.05	0.071	0.4192	-0.009	0.4321	42.6822	11.243	19.6935

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'A' and (resid -1 through 296 )
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 297 through 554 )
3	X-RAY DIFFRACTION	3	chain 'B' and (resid 4 through 83 )
4	X-RAY DIFFRACTION	4	chain 'B' and (resid 84 through 104 )
5	X-RAY DIFFRACTION	5	chain 'B' and (resid 105 through 238 )
6	X-RAY DIFFRACTION	6	chain 'B' and (resid 239 through 269 )
7	X-RAY DIFFRACTION	7	chain 'B' and (resid 270 through 363 )
8	X-RAY DIFFRACTION	8	chain 'B' and (resid 364 through 428 )

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