PDB-6c0p: Crystal structure of HIV-1 E138K mutant reverse transcriptase in ...

ID or keywords:

Entry

Database: PDB / ID: 6c0p

Title

Crystal structure of HIV-1 E138K mutant reverse transcriptase in complex with non-nucleoside inhibitor 25a

Components

Reverse transcriptase p51 subunit
Reverse transcriptase/ribonuclease H

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 / host multivesicular body / DNA integration / viral genome integration into host DNA / RNA-directed DNA polymerase / establishment of integrated proviral latency ...
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: 2.05 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	Jan 1, 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 / Refinement description Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	6c0p.cif.gz	446.3 KB	Display	PDBx/mmCIF format
PDB format	pdb6c0p.ent.gz	364.8 KB	Display	PDB format
PDBx/mmJSON format	6c0p.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	6c0p_validation.pdf.gz	847.5 KB	Display	wwPDB validaton report
Full document	6c0p_full_validation.pdf.gz	874.3 KB	Display
Data in XML	6c0p_validation.xml.gz	46.6 KB	Display
Data in CIF	6c0p_validation.cif.gz	66.5 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/c0/6c0p ftp://data.pdbj.org/pub/pdb/validation_reports/c0/6c0p	HTTPS FTP

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Related structure data

Related structure data	6c0jC 6c0kC 6c0lC 6c0nC 6c0oC 6c0rC 6cgfC 6dufC 6dugC 6duhC 4g1qS C: citing same article (ref.) S: Starting model for refinement
Similar structure data	6c0o-d 4idk-d 6x4c-d 4ig3-d 2hny-d 4kfb-d 4i2p-d 4ifv-d 4ify-d 6cgf-d 6x47-d 6c0n-d 2zd1-d 6c0j-d 6ul5-d 6eli-d 5cyq-d 4g1q-d 6x4f-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: Reverse transcriptase p51 subunit

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)	162.832, 73.193, 109.308
Angle α, β, γ (deg.)	90.00, 100.19, 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 / Pr160Gag-Pol 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 Gene: gag-pol / Production host: Escherichia coli (E. coli) / References: UniProt: P03366, RNA-directed DNA polymerase
#2: Protein	Reverse transcriptase p51 subunit / Pr160Gag-Pol Mass: 50039.555 Da / Num. of mol.: 1 / Mutation: E138K, 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 (E. coli) / References: UniProt: P03366, RNA-directed DNA polymerase

#1: Protein

Reverse transcriptase/ribonuclease H / Pr160Gag-Pol

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
Gene: gag-pol / Production host:

Escherichia coli (E. coli) / References: UniProt: P03366, RNA-directed DNA polymerase

#2: Protein

Reverse transcriptase p51 subunit / Pr160Gag-Pol

Mass: 50039.555 Da / Num. of mol.: 1 / Mutation: E138K, 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 (E. coli) / References: UniProt: P03366, RNA-directed DNA polymerase

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Non-polymers , 6 types, 672 molecules

#3: Chemical	ChemComp-K5C / 4-({4-[(4-{4-[(E)-2-cyanoethenyl]-2,6-dimethylphenoxy}thieno[3,2-d]pyrimidin-2-yl)amino]piperidin-1-yl}methyl)benzene-1-sulfonamide Mass: 574.717 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂₉H₃₀N₆O₃S₂ / 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-SO4 / SULFATE ION Mass: 96.063 Da / Num. of mol.: 9 / Source method: obtained synthetically / Formula: SO₄
#6: Chemical	... ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 27 / Source method: obtained synthetically / Formula: C₂H₆O₂
#7: Chemical	ChemComp-DMS / DIMETHYL SULFOXIDE Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂H₆OS / Comment: DMSO, precipitant*YM
#8: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 633 / 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: 2.81 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: Jun 10, 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: 2.05→50 Å / Num. obs: 76514 / % possible obs: 96.1 % / Redundancy: 3.5 % / CC_1/2: 0.999 / R_merge(I) obs: 0.03522 / R_rim(I) all: 0.04145 / Net I/σ(I): 15.83
Reflection shell	Resolution: 2.05→2.17 Å / Redundancy: 3.4 % / R_merge(I) obs: 1.202 / Mean I/σ(I) obs: 0.97 / Num. unique obs: 12221 / CC_1/2: 0.377 / R_rim(I) all: 1.415 / % possible all: 95.1

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Processing

Software

Name	Version	Classification
PHENIX	(1.12_2829)	refinement
XDS	June 1, 2017	data reduction
XDS	June 1, 2017	data scaling
PHENIX	1.12_2829	phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 4G1Q

4g1q

Resolution: 2.05→48.84 Å / SU ML: 0.31 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 25.34

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.2154	3826	5 %	Random selection
R_work	0.1801	-	-	-
obs	0.1819	76514	96.12 %	-

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å

Refinement step

Cycle: LAST / Resolution: 2.05→48.84 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	7926	0	198	633	8757

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.005	8451
X-RAY DIFFRACTION	f_angle_d	0.638	11452
X-RAY DIFFRACTION	f_dihedral_angle_d	14.289	5038
X-RAY DIFFRACTION	f_chiral_restr	0.046	1223
X-RAY DIFFRACTION	f_plane_restr	0.004	1428

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 (%)
2.05-2.076	0.3713	132	0.3526	2513	X-RAY DIFFRACTION	89
2.076-2.1033	0.3774	141	0.3298	2681	X-RAY DIFFRACTION	97
2.1033-2.1321	0.3514	141	0.3071	2687	X-RAY DIFFRACTION	97
2.1321-2.1626	0.3076	141	0.2912	2676	X-RAY DIFFRACTION	97
2.1626-2.1948	0.3373	143	0.2928	2704	X-RAY DIFFRACTION	97
2.1948-2.2291	0.2861	143	0.2645	2729	X-RAY DIFFRACTION	97
2.2291-2.2657	0.3248	139	0.2673	2641	X-RAY DIFFRACTION	96
2.2657-2.3047	0.3348	139	0.2498	2642	X-RAY DIFFRACTION	95
2.3047-2.3467	0.2671	143	0.2377	2705	X-RAY DIFFRACTION	97
2.3467-2.3918	0.3072	142	0.2295	2703	X-RAY DIFFRACTION	97
2.3918-2.4406	0.2436	144	0.2172	2732	X-RAY DIFFRACTION	97
2.4406-2.4937	0.2726	141	0.2113	2682	X-RAY DIFFRACTION	97
2.4937-2.5517	0.261	143	0.205	2713	X-RAY DIFFRACTION	97
2.5517-2.6155	0.2626	143	0.2046	2734	X-RAY DIFFRACTION	98
2.6155-2.6862	0.2816	142	0.2049	2693	X-RAY DIFFRACTION	97
2.6862-2.7652	0.2738	144	0.1983	2739	X-RAY DIFFRACTION	98
2.7652-2.8545	0.229	142	0.1914	2695	X-RAY DIFFRACTION	97
2.8545-2.9565	0.2507	143	0.1836	2718	X-RAY DIFFRACTION	97
2.9565-3.0748	0.2352	142	0.1901	2698	X-RAY DIFFRACTION	96
3.0748-3.2148	0.2512	138	0.184	2616	X-RAY DIFFRACTION	94
3.2148-3.3842	0.2428	134	0.1819	2542	X-RAY DIFFRACTION	91
3.3842-3.5962	0.2011	145	0.1699	2765	X-RAY DIFFRACTION	98
3.5962-3.8737	0.2204	145	0.1588	2740	X-RAY DIFFRACTION	98
3.8737-4.2634	0.1509	144	0.1475	2749	X-RAY DIFFRACTION	97
4.2634-4.8798	0.1656	144	0.1442	2728	X-RAY DIFFRACTION	97
4.8798-6.1461	0.2051	141	0.1767	2677	X-RAY DIFFRACTION	94
6.1461-48.8534	0.19	147	0.1779	2786	X-RAY DIFFRACTION	96

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	3.3855	-0.3212	-1.7952	2.7433	0.3708	2.5849	0.2055	-0.1933	0.1188	1.0182	-0.1393	0.3889	-0.0188	0.0271	-0.04	1.1809	-0.1291	0.1704	0.7418	-0.014	0.504	46.8769	-14.7213	70.4475
2	0.8886	0.3331	-0.3948	0.3714	1.1437	7.2825	0.2162	-0.0831	0.1292	0.2593	-0.0592	0.5628	0.5882	-0.6754	-0.1622	0.966	-0.0054	0.113	0.8634	0.047	0.7201	40.0488	-17.3425	59.0569
3	0.3293	0.0691	-1.057	1.232	1.4611	5.5478	0.1767	-0.1959	-0.1126	0.5308	0.1056	0.079	0.5853	-0.0064	-0.1915	0.8134	0.0112	-0.0936	0.6423	0.0605	0.51	54.1797	-23.1467	52.9425
4	3.404	0.2641	1.2291	2.105	-0.4882	2.9978	0.4073	-1.0595	-1.1115	0.4479	0.2597	0.9498	0.3075	-0.8946	-0.2937	0.6578	-0.1195	-0.0074	0.7622	0.2945	0.9374	30.6648	-21.2341	26.6266
5	4.426	-2.597	1.4444	1.957	-0.8392	1.0669	0.1059	0.0677	-0.1721	-0.0573	0.059	0.1746	0.2087	-0.1057	-0.157	0.4291	-0.0606	0.0201	0.4464	-0.0338	0.4778	23.9886	1.3338	7.2196
6	6.8268	1.2259	1.2954	4.3684	0.5914	5.6874	-0.1689	-0.4887	-0.2056	0.1887	0.2124	0.4125	-0.2544	-0.3886	-0.0609	0.296	0.0337	0.0755	0.5033	0.0976	0.5181	14.2625	8.9448	6.6819
7	5.7422	-0.2362	1.2305	5.9926	0.3415	5.2822	-0.0779	-0.0272	0.3267	0.3625	-0.0684	-0.1192	-0.2958	0.4361	0.0331	0.5153	-0.0624	-0.015	0.4222	0.0433	0.3138	56.6063	2.0097	36.6821
8	3.3755	2.6579	-3.234	8.4531	-8.9278	9.4721	-0.0585	-0.4722	1.3246	1.2165	-0.2603	0.4633	-2.1887	0.9108	0.5199	1.3798	-0.3086	-0.1854	0.9382	0.0228	1.1381	55.4658	27.0927	33.6961
9	2.3905	-0.1034	0.5248	5.3098	-1.8429	2.04	-0.1132	0.0479	0.5147	0.5839	-0.0929	-0.674	-0.4862	0.5979	0.0501	0.7817	-0.2327	-0.0849	0.6919	0.0121	0.5962	62.0137	13.2733	34.3994
10	5.2693	-0.9365	4.9223	0.1689	-0.0423	4.3338	-0.2313	0.803	-0.2059	0.1831	0.2026	-0.2961	-0.4199	1.0323	-0.2084	0.6209	-0.1851	-0.0701	1.1655	0.1841	0.8539	58.0701	22.3491	13.7814
11	2.5073	-0.6823	2.149	2.4452	-1.4879	3.5798	-0.241	0.0845	0.3263	0.3914	-0.0253	-0.144	-0.4187	-0.0237	0.318	0.5304	-0.0468	0.0821	0.4254	-0.0316	0.4429	36.4169	19.6772	13.094

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'A' and (resid -1 through 59 )
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 60 through 96 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 97 through 226 )
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 227 through 383 )
5	X-RAY DIFFRACTION	5	chain 'A' and (resid 384 through 473 )
6	X-RAY DIFFRACTION	6	chain 'A' and (resid 474 through 554 )
7	X-RAY DIFFRACTION	7	chain 'B' and (resid 4 through 83 )
8	X-RAY DIFFRACTION	8	chain 'B' and (resid 84 through 104 )
9	X-RAY DIFFRACTION	9	chain 'B' and (resid 105 through 194 )
10	X-RAY DIFFRACTION	10	chain 'B' and (resid 195 through 253 )
11	X-RAY DIFFRACTION	11	chain 'B' and (resid 254 through 428 )

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