PDB-3r4b: Crystal Structure of Wild-type HIV-1 Protease in Complex With TMC...

ID or keywords:

Entry

Database: PDB / ID: 3r4b

Title

Crystal Structure of Wild-type HIV-1 Protease in Complex With TMC310911

Components

HIV-1 protease

Keywords

HYDROLASE/HYDROLASE INHIBITOR / drug resistance / drug design / protease inhibitors / AIDS / aspartyl protease / HYDROLASE-HYDROLASE INHIBITOR complex

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 1

Method

X-RAY DIFFRACTION /

MOLECULAR REPLACEMENT / Resolution: 1.9 Å

Authors

Schiffer, C.A. / Nalam, M.N.L.

Citation

Journal: Antimicrob.Agents Chemother. / Year: 2011
Title: TMC310911, a Novel Human Immunodeficiency Virus Type 1 Protease Inhibitor, Shows In Vitro an Improved Resistance Profile and Higher Genetic Barrier to Resistance Compared with Current Protease Inhibitors.
Authors: Dierynck, I. / Van Marck, H. / Van Ginderen, M. / Jonckers, T.H. / Nalam, M.N. / Schiffer, C.A. / Raoof, A. / Kraus, G. / Picchio, G.

History

Deposition	Mar 17, 2011	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Sep 21, 2011	Provider: repository / Type: Initial release
Revision 1.1	Nov 30, 2011	Group: Database references
Revision 1.2	Nov 8, 2017	Group: Refinement description / Category: software
Revision 1.3	Sep 13, 2023	Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description / Structure summary Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / entity / pdbx_entity_nonpoly / pdbx_initial_refinement_model / struct_ref_seq_dif / struct_site Item: _chem_comp.name / _database_2.pdbx_DOI ..._chem_comp.name / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity.pdbx_description / _pdbx_entity_nonpoly.name / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	3r4b.cif.gz	101 KB	Display	PDBx/mmCIF format
PDB format	pdb3r4b.ent.gz	79.1 KB	Display	PDB format
PDBx/mmJSON format	3r4b.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	3r4b_validation.pdf.gz	910.7 KB	Display	wwPDB validaton report
Full document	3r4b_full_validation.pdf.gz	916.6 KB	Display
Data in XML	3r4b_validation.xml.gz	12.1 KB	Display
Data in CIF	3r4b_validation.cif.gz	15.9 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/r4/3r4b ftp://data.pdbj.org/pub/pdb/validation_reports/r4/3r4b	HTTPS FTP

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Related structure data

Related structure data	1f7aS S: Starting model for refinement
Similar structure data	1mtb-d 6oxz-d 2uxz-d 2psv-d 4f75-d 2nxl-d 4mc1-d 3ttp-d 1yth-d 4njt-1 5kr2-3 3bgc-d 2qi0-d 1d4j-d 3s43-d 6opu-d 6dh7-d 2nxd-d 1qbt-d 3th9-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	#6 - Jun 2000 HIV-1 Protease similarity (1) #163 - Jul 2013 HIV Capsid similarity (1)

Deposited unit

A: HIV-1 protease

B: HIV-1 protease

hetero molecules

22.5 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)	50.681, 58.369, 61.116
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	19
Space group name H-M	P2₁2₁2₁

#1: Protein	HIV-1 protease Mass: 10815.790 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Strain: HXB2 / Gene: gag-pol, pol / Plasmid: pXC35 / Production host: Escherichia coli (E. coli) / Strain (production host): TAP106 / References: UniProt: Q90K99, UniProt: P03369*PLUS
#2: Chemical	ChemComp-74T / (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl {(2S,3R)-4-[({2-[(1-cyclopentylpiperidin-4-yl)amino]-1,3-benzothiazol-6-yl}sulfonyl)(2-methylpropyl)amino]-3-hydroxy-1-p henylbutan-2-yl}carbamate / TMC310911 Mass: 755.987 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₃₈H₅₃N₅O₇S₂
#3: Chemical	ChemComp-PO4 / PHOSPHATE ION Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO₄
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 96 / 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: 2.09 Å³/Da / Density % sol: 41.13 %
Crystal grow	Temperature: 295 K / Method: vapor diffusion, hanging drop / pH: 6.2 Details: 24-29% ammonium sulfate, 63 mM sodium citrate, 126 mM phosphate, pH 6.2, VAPOR DIFFUSION, HANGING DROP, temperature 295K

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Data collection

Diffraction

Mean temperature: 193 K

Diffraction source

Source:

ROTATING ANODE / Type: RIGAKU / Wavelength: 1.5418

Detector

Type: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Nov 9, 2005

Radiation

Protocol: SINGLE WAVELENGTH / Scattering type: x-ray

Radiation wavelength

Wavelength: 1.5418 Å / Relative weight: 1

Reflection

Resolution: 1.9→50 Å / Num. obs: 14669 / % possible obs: 98.6 % / Redundancy: 6.6 % / R_merge(I) obs: 0.054 / Χ²: 1.016 / Net I/σ(I): 13.9

Reflection shell

Resolution (Å)	Redundancy (%)	R_merge(I) obs	Num. unique all	Χ²	Diffraction-ID	% possible all
1.9-1.97	5.9	0.323	1412	1.029	1	96.5
1.97-2.05	6.6	0.267	1417	1.083	1	97.5
2.05-2.14	6.7	0.204	1417	1	1	97.9
2.14-2.25	6.7	0.146	1426	0.96	1	97.8
2.25-2.39	6.7	0.116	1456	1.001	1	98.9
2.39-2.58	6.8	0.091	1459	0.977	1	98.7
2.58-2.84	6.8	0.071	1467	1.046	1	99.4
2.84-3.25	6.7	0.051	1493	1.062	1	99.6
3.25-4.09	6.8	0.037	1511	0.964	1	100
4.09-50	6.5	0.027	1611	1.044	1	99.7

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Processing

Software

Name	Version	Classification
SCALEPACK		data scaling
REFMAC		refinement
PDB_EXTRACT	3.1	data extraction
DENZO		data reduction
AMoRE		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1F7A

1f7a

Resolution: 1.9→42.22 Å / Cor.coef. F_o:F_c: 0.959 / Cor.coef. F_o:F_c free: 0.94 / WR_factor R_free: 0.2217 / WR_factor R_work: 0.1751 / Occupancy max: 1 / Occupancy min: 0.5 / FOM work R set: 0.8406 / SU B: 7.484 / SU ML: 0.113 / SU R Cruickshank DPI: 0.18 / SU R_free: 0.1583 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.18 / ESU R Free: 0.158 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT U VALUES : WITH TLS ADDED

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.2269	738	5 %	RANDOM
R_work	0.1794	-	-	-
obs	0.1818	14635	98.67 %	-

Solvent computation

Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK

Displacement parameters

B_iso max: 74.97 Å² / B_iso mean: 39.0945 Å² / B_iso min: 23.71 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-1.49 Å²	0 Å²	0 Å²
2-	-	-0.18 Å²	0 Å²
3-	-	-	1.68 Å²

Refinement step

Cycle: LAST / Resolution: 1.9→42.22 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1494	0	57	96	1647

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.009	0.022	1746
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.02	1184
X-RAY DIFFRACTION	r_angle_refined_deg	1.527	2.056	2399
X-RAY DIFFRACTION	r_angle_other_deg	0.808	3	2929
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.349	5	218
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	42.46	25	60
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	12.179	15	280
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	21.181	15	9
X-RAY DIFFRACTION	r_chiral_restr	0.082	0.2	283
X-RAY DIFFRACTION	r_gen_planes_refined	0.005	0.021	1895
X-RAY DIFFRACTION	r_gen_planes_other	0.002	0.02	314

LS refinement shell

Resolution: 1.9→1.949 Å / Total num. of bins used: 20

	R_factor	Num. reflection	% reflection
R_free	0.325	57	-
R_work	0.198	976	-
all	-	1033	-
obs	-	-	95.65 %

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	4.7765	-3.2275	-0.1848	3.5637	-0.2518	3.7197	-0.0977	-0.0031	-0.3217	0.2148	0.0811	0.3228	0.1797	-0.0498	0.0166	0.0723	-0.0059	0.0363	0.035	0.0236	0.0645	19.8265	17.6381	22.905
2	6.8446	0.2985	-0.9635	2.9542	1.8915	2.0649	-0.0147	-0.4418	0.2049	0.1137	-0.0152	0.104	-0.0525	-0.0541	0.0299	0.1365	0.0359	0.0153	0.1287	-0.0193	0.0113	20.9631	25.8142	29.1044
3	5.5896	-1.2955	0.5457	4.8416	-1.0926	2.5917	0.0443	-0.0803	-0.2272	-0.0484	0.0798	0.3479	0.0427	-0.1708	-0.1241	0.0409	0.0011	0.0316	0.0224	0.0032	0.1294	13.9584	27.5823	18.794
4	4.4377	1.7415	1.8888	5.6166	-1.5826	1.9179	-0.1123	-0.0239	0.0323	0.0381	0.0046	-0.1167	-0.1089	-0.016	0.1076	0.0415	0.007	-0.0137	0.061	-0.0111	0.0413	26.5014	27.5683	18.3433
5	21.459	-5.8358	-2.3654	2.45	-1.8865	7.6846	0.4413	0.8659	-0.8245	-0.0269	-0.0479	0.3824	-0.3118	-0.7116	-0.3935	0.1117	-0.0023	-0.0077	0.1856	-0.0527	0.3792	1.3717	21.9612	16.9368
6	6.0036	4.5673	-0.9513	8.826	-0.9148	6.0224	0.1355	-0.0953	-0.2305	0.1188	-0.2488	-0.9086	-0.2204	0.5026	0.1133	0.0936	-0.0129	-0.075	0.1268	0.0662	0.1808	39.2454	31.1845	23.2405
7	9.1716	1.3745	-2.0051	5.0806	1.4394	3.0391	0.1939	0.4686	0.1518	0.0098	-0.0541	-0.0306	0.2287	-0.4045	-0.1398	0.1411	0.0091	-0.0102	0.198	0.0796	0.158	0.2783	34.5257	12.9471
8	7.0502	2.0494	1.7157	1.4289	2.0499	4.6577	0.0534	0.1242	0.0049	-0.1622	0.0091	-0.1719	-0.131	0.2965	-0.0625	0.1533	0.009	0.0164	0.1338	0.0746	0.13	39.5058	31.0711	9.2359
9	19.4931	-11.3915	-1.6648	12.4193	-0.9708	0.9872	0.0145	0.0685	-0.0023	0.2915	0.0547	0.4538	-0.1182	-0.0457	-0.0692	0.105	-0.0155	0.0191	0.083	-0.0039	0.0717	13.7851	40.1504	11.3304
10	14.4173	-0.6096	-3.8909	0.0531	0.4749	4.5795	0.0215	0.3216	-0.2946	0.0023	-0.0072	0.0045	0.0412	0.0232	-0.0143	0.0794	0.0138	0.0119	0.0271	0.0012	0.0453	25.8941	31.1363	3.8735
11	10.3278	-8.1888	7.2115	13.5761	-11.2448	9.5661	0.8289	0.5706	-0.6836	-0.7665	-0.4229	0.8034	0.5794	0.475	-0.406	0.1614	0.0339	-0.1356	0.1276	0.0237	0.3134	10.6531	29.6805	11.7389
12	0.9696	1.5752	-2.9408	4.8959	-2.5687	11.1287	0.1679	0.0683	0.1129	0.051	0.0272	0.3851	-0.8071	-0.1901	-0.1951	0.1118	-0.0002	-0.0207	0.1037	0.0112	0.0913	29.1876	33.521	14.1427
13	8.1578	-3.6595	-4.5659	1.8823	1.4259	4.1946	-0.3672	-0.6177	-0.3026	0.1937	0.3998	0.2324	0.0917	0.037	-0.0326	0.1295	0.0398	0.0192	0.1337	0.0561	0.2006	11.9652	29.1062	26.786
14	3.9078	0.8751	2.6547	3.5909	-0.3584	2.7297	0.0304	0.082	-0.2412	0.0231	0.0356	0.0337	0.0079	0.1012	-0.0659	0.0516	0.0016	0.0092	0.0497	-0.0055	0.047	28.7627	19.5127	19.0706
15	7.7188	7.6663	-9.931	12.3176	-14.2851	19.5987	0.4163	-0.067	0.3789	0.207	0.1845	0.366	-0.243	-0.0841	-0.6008	0.1184	0.0756	0.0314	0.1528	0.0375	0.3328	1.8463	37.0717	18.5133
16	4.0187	-5.1151	3.9342	10.9155	-14.0701	22.5171	0	0.1525	-0.2728	-0.0696	-0.567	-0.0869	0.1041	0.8755	0.567	0.059	0.0247	0.0395	0.1804	0.0157	0.1686	38.4913	25.4855	9.0416
17	15.0695	-16.1382	-0.9219	18.6094	-0.2662	11.3347	-0.2083	0.3017	0.6564	0.253	-0.0381	-1.0308	0.5331	0.5465	0.2464	0.111	0.0542	0.0319	0.1844	0.0231	0.2545	2.9082	23.1718	23.9452
18	14.8866	-2.2476	-1.0742	5.7261	3.4112	15.16	-0.2597	0.0397	0.5444	0.4886	0.113	-0.257	0.306	0.0334	0.1467	0.0907	-0.0107	-0.068	0.0165	0.015	0.1805	37.534	24.3592	23.9731
19	0.8614	1.1816	-1.8422	8.6622	-6.0765	7.6409	-0.0282	-0.1765	0.2725	0.0349	0.1979	0.2005	0.2268	0.0925	-0.1697	0.0893	0.0369	0.0231	0.1618	0.0056	0.2325	4.1107	28.7108	25.0408
20	1.2626	0.1471	1.1301	3.3352	-2.6744	6.6854	-0.1267	-0.012	-0.0413	0.0982	-0.1478	-0.2853	0.0199	0.0902	0.2745	0.0664	-0.0002	0.0162	0.0941	0.0121	0.0871	35.782	21.9236	17.9443
21	2.7896	0.3281	-0.883	3.4942	1.7286	10.9791	-0.0997	-0.2064	0.0236	0.2107	0.3038	0.1858	0.0261	0.3713	-0.2041	0.0676	0.0351	0.0112	0.1138	0.0309	0.0914	20.2107	31.0858	13.6511

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	A	1 - 5
2	X-RAY DIFFRACTION	1	A	94 - 99
3	X-RAY DIFFRACTION	1	A	6 - 10
4	X-RAY DIFFRACTION	2	B	1 - 5
5	X-RAY DIFFRACTION	2	B	94 - 99
6	X-RAY DIFFRACTION	2	B	6 - 10
7	X-RAY DIFFRACTION	3	A	21 - 32
8	X-RAY DIFFRACTION	4	B	21 - 32
9	X-RAY DIFFRACTION	5	A	11 - 20
10	X-RAY DIFFRACTION	6	B	11 - 20
11	X-RAY DIFFRACTION	7	A	33 - 43
12	X-RAY DIFFRACTION	8	B	33 - 43
13	X-RAY DIFFRACTION	9	A	44 - 56
14	X-RAY DIFFRACTION	10	B	44 - 56
15	X-RAY DIFFRACTION	11	A	77 - 85
16	X-RAY DIFFRACTION	12	B	77 - 85
17	X-RAY DIFFRACTION	13	A	86 - 93
18	X-RAY DIFFRACTION	14	B	86 - 93
19	X-RAY DIFFRACTION	15	A	57 - 62
20	X-RAY DIFFRACTION	16	B	57 - 62
21	X-RAY DIFFRACTION	17	A	63 - 68
22	X-RAY DIFFRACTION	18	B	63 - 68
23	X-RAY DIFFRACTION	19	A	69 - 76
24	X-RAY DIFFRACTION	20	B	69 - 76
25	X-RAY DIFFRACTION	21	A	200

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