PDB-4obd: Crystal Structure of Nelfinavir-Resistant, Inactive HIV-1 Proteas...

ID or keywords:

Entry

Database: PDB / ID: 4obd

Title

Crystal Structure of Nelfinavir-Resistant, Inactive HIV-1 Protease (D30N/N88D) in Complex with the p1-p6 substrate variant (L449F/S451N)

Components

HIV-1 Protease
p1-p6 peptide

Keywords

HYDROLASE / Co-evolution / Resistance / Hydrolases

Function / homology

Function and homology information

viral budding via host ESCRT complex / 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 ...
Similarity search - Function

Gag protein p6 / Gag protein p6 / : / gag protein p24 N-terminal domain / 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

Human immunodeficiency virus 1

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT /

molecular replacement / Resolution: 1.9 Å

Authors

Kolli, M.

Citation

Journal: J.Virol. / Year: 2014
Title: HIV-1 protease-substrate coevolution in nelfinavir resistance.
Authors: Kolli, M. / Ozen, A. / Kurt-Yilmaz, N. / Schiffer, C.A.

History

Deposition	Jan 7, 2014	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Nov 26, 2014	Provider: repository / Type: Initial release
Revision 1.1	Nov 22, 2017	Group: Refinement description / Category: software
Revision 1.2	Sep 20, 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 / struct_ref_seq_dif / struct_site Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _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

-
Download

PDBx/mmCIF format	4obd.cif.gz	124.1 KB	Display	PDBx/mmCIF format
PDB format	pdb4obd.ent.gz	97.3 KB	Display	PDB format
PDBx/mmJSON format	4obd.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

-
Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/ob/4obd ftp://data.pdbj.org/pub/pdb/validation_reports/ob/4obd	HTTPS FTP

-
Related structure data

Related structure data	4obfC 4obgC 4obhC 4objC 4obkC 1t3rS C: citing same article (ref.) S: Starting model for refinement
Similar structure data	4qj8-1 6ixd-d 3em4-2 4coe-d 1kj4-1 3kf0-d 3zps-d 3kdb-d 4mc9-d 3oxx-1 3k4v-2 8hvp-d 4zip-d 6dil-d 4a6b-d 4qj2-2 5dgu-d 3ndu-2 1d4h-d 3cyx-d Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

Related structure data

C: citing same article (ref.)

S: Starting model for refinement

Similar structure data

-
Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#6 - Jun 2000 HIV-1 Protease similarity (1) #226 - Oct 2018 Aminoglycoside Antibiotics and Resistance similarity (1) #163 - Jul 2013 HIV Capsid similarity (3) #87 - Mar 2007 Zinc Fingers similarity (2)

Deposited unit

A: HIV-1 Protease

B: HIV-1 Protease

C: HIV-1 Protease

D: HIV-1 Protease

E: p1-p6 peptide

F: p1-p6 peptide

hetero molecules

46 kDa, 6 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: HIV-1 Protease

B: HIV-1 Protease

E: p1-p6 peptide

hetero molecules

defined by author&software
23.1 kDa, 3 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

C: HIV-1 Protease

D: HIV-1 Protease

F: p1-p6 peptide

hetero molecules

defined by author&software
22.9 kDa, 3 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	51.474, 59.545, 59.362
Angle α, β, γ (deg.)	90.00, 98.60, 90.00
Int Tables number	4
Space group name H-M	P12₁1

#1: Protein	HIV-1 Protease / PR / Retropepsin Mass: 10814.804 Da / Num. of mol.: 4 / Mutation: Q7K, D25N, D30N, N88D Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus type 1 / Strain: group M subtype B (isolate ARV2/SF2) / Gene: gag-pol / Plasmid: pXC35 / Production host: Escherichia coli (E. coli) / Strain (production host): TAP106 / References: UniProt: P03369, HIV-1 retropepsin
#2: Protein/peptide	p1-p6 peptide Mass: 1234.366 Da / Num. of mol.: 2 / Fragment: UNP residues 446-455 / Mutation: L6F, S8N / Source method: obtained synthetically / Source: (synth.) Human immunodeficiency virus 1 / References: UniProt: P03349
#3: Chemical	ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₃H₈O₃
#4: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₂H₆O₂
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 83 / Source method: isolated from a natural source / Formula: H₂O

-
Experiment

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

-
Sample preparation

Crystal	Density Matthews: 1.97 Å³/Da / Density % sol: 37.55 %
Crystal grow	Temperature: 295 K / Method: vapor diffusion, hanging drop / pH: 6.5 Details: 24% PEG 5000, 0.3M ammonium sulfate, 0.5M MES monohydrate, pH 6.5, VAPOR DIFFUSION, HANGING DROP, temperature 295K

-
Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: APS / Beamline: 14-ID-B / Wavelength: 1.033 Å
Detector	Type: MAR CCD 165 mm / Detector: CCD / Date: Mar 9, 2009 / Details: Mirrors
Radiation	Monochromator: Si(111) double-crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.033 Å / Relative weight: 1
Reflection	Resolution: 1.68→50 Å / Num. obs: 39171 / % possible obs: 98.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 2 / Redundancy: 3.8 % / R_sym value: 0.064 / Net I/σ(I): 16.85

-
Phasing

Phasing

Method:

molecular replacement

Phasing MR

R_factor: 45.42 / Model details: Phaser MODE: MR_AUTO

	Highest resolution	Lowest resolution
Rotation	2.5 Å	38.69 Å
Translation	2.5 Å	38.69 Å

-
Processing

Software

Name	Version	Classification
DENZO		data reduction
SCALEPACK		data scaling
PHASER	2.1.4	phasing
REFMAC	5.5.0102	refinement
PDB_EXTRACT	3.14	data extraction
BioCARS-developed	GUI	data collection
HKL-2000		data reduction
HKL-2000		data scaling

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: PDB entry 1T3R

1t3r

Resolution: 1.9→40 Å / Cor.coef. F_o:F_c: 0.946 / Cor.coef. F_o:F_c free: 0.91 / Occupancy max: 1 / Occupancy min: 0.5 / SU B: 5.129 / SU ML: 0.119 / Isotropic thermal model: Overall / Cross valid method: THROUGHOUT / ESU R: 0.182 / ESU R Free: 0.166 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.24797	1412	5.1 %	RANDOM
R_work	0.19638	-	-	-
obs	0.19905	26425	98.86 %	-

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 mean: 30.998 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-3.24 Å²	0 Å²	-0.21 Å²
2-	-	1.02 Å²	0 Å²
3-	-	-	2.18 Å²

Refinement step

Cycle: LAST / Resolution: 1.9→40 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	3053	0	18	83	3154

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.008	0.019	3131
X-RAY DIFFRACTION	r_bond_other_d	0.003	0.02	3103
X-RAY DIFFRACTION	r_angle_refined_deg	1.534	1.98	4264
X-RAY DIFFRACTION	r_angle_other_deg	0.726	3	7087
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	7.358	5	409
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	42.266	24.771	109
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	13.977	15	493
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	16.702	15	15
X-RAY DIFFRACTION	r_chiral_restr	0.101	0.2	512
X-RAY DIFFRACTION	r_gen_planes_refined	0.011	0.021	3538
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	663
X-RAY DIFFRACTION	r_nbd_refined
X-RAY DIFFRACTION	r_nbd_other
X-RAY DIFFRACTION	r_nbtor_refined
X-RAY DIFFRACTION	r_nbtor_other
X-RAY DIFFRACTION	r_xyhbond_nbd_refined
X-RAY DIFFRACTION	r_xyhbond_nbd_other
X-RAY DIFFRACTION	r_metal_ion_refined
X-RAY DIFFRACTION	r_metal_ion_other
X-RAY DIFFRACTION	r_symmetry_vdw_refined
X-RAY DIFFRACTION	r_symmetry_vdw_other
X-RAY DIFFRACTION	r_symmetry_hbond_refined
X-RAY DIFFRACTION	r_symmetry_hbond_other
X-RAY DIFFRACTION	r_symmetry_metal_ion_refined
X-RAY DIFFRACTION	r_symmetry_metal_ion_other
X-RAY DIFFRACTION	r_mcbond_it	3.215	2.622	1648
X-RAY DIFFRACTION	r_mcbond_other	3.216	2.621	1647
X-RAY DIFFRACTION	r_mcangle_it	4.382	3.906	2050
X-RAY DIFFRACTION	r_mcangle_other
X-RAY DIFFRACTION	r_scbond_it	3.801	3.004	1483
X-RAY DIFFRACTION	r_scbond_other
X-RAY DIFFRACTION	r_scangle_it
X-RAY DIFFRACTION	r_scangle_other
X-RAY DIFFRACTION	r_long_range_B_refined
X-RAY DIFFRACTION	r_long_range_B_other
X-RAY DIFFRACTION	r_rigid_bond_restr
X-RAY DIFFRACTION	r_sphericity_free
X-RAY DIFFRACTION	r_sphericity_bonded

LS refinement shell

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

	R_factor	Num. reflection	% reflection
R_free	0.24	89	-
R_work	0.201	1981	-
obs	-	-	99.81 %

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	2.2307	1.9797	1.4829	2.2003	0.2432	3.5844	-0.1901	0.2104	0.0157	-0.1318	0.2339	0.0329	-0.2158	0.0183	-0.0438	0.1205	-0.0186	-0.0034	0.0525	0.0344	0.0355	-5.4561	3.8512	-12.2458
2	8.095	-1.3823	-4.0686	0.2891	0.7097	2.0492	0.0328	-0.2704	0.2903	0.0068	0.0787	0.0642	-0.0148	0.1448	-0.1115	0.0824	-0.006	0.0299	0.0329	0.0529	0.2551	-6.0752	7.0953	0.6419
3	7.0485	-0.3763	-0.9459	1.7083	0.1684	0.1353	-0.0585	0.4493	-0.2477	0.0307	0.0581	-0.4311	0.0071	-0.053	0.0004	0.0608	-0.0212	0.0039	0.0658	-0.0436	0.1274	-4.8511	-9.2293	-12.0064
4	0.9892	-0.3408	-1.4816	0.2311	0.7978	2.948	0.079	0.1013	0.0623	0.0408	0.0181	-0.021	0.0673	-0.0232	-0.0971	0.1404	-0.0017	-0.011	0.054	0.013	0.0388	-11.2311	-4.4137	-2.6257
5	7.4826	1.3068	1.2932	7.7675	1.2478	1.1925	0.0593	0.0571	0.1371	0.2367	-0.0422	0.2915	-0.1224	-0.2372	-0.0171	0.0552	0.0231	0.0255	0.1035	0.0196	0.0193	-25.1982	-10.265	3.0178
6	2.7612	-1.7272	0.4773	1.1237	-0.0451	2.1683	0.0382	0.1244	-0.0025	0.006	-0.0664	-0.0053	-0.1079	0.036	0.0282	0.1604	-0.0122	-0.0172	0.0687	-0.0193	0.0318	0.6411	-2.8926	-1.9581
7	4.863	-1.3085	-2.2346	3.7306	2.7775	2.4312	-0.1553	-0.3462	-0.0884	-0.0543	0.2846	-0.2376	0.0171	0.301	-0.1293	0.0387	0.0542	0.0156	0.1469	0.0157	0.0302	15.1126	-6.8008	5.6847
8	6.9738	1.5346	1.0726	1.6486	0.4825	0.3126	-0.018	0.0452	-0.0895	0.0551	-0.016	0.0421	0.0182	0.0188	0.034	0.0796	-0	0.0074	0.0501	0.0024	0.0567	-13.229	-17.0493	4.1479
9	6.153	2.4415	0.9522	1.7901	-0.8238	1.9116	0.0504	-0.2035	0.0097	-0.0209	-0.0822	-0.01	0.0591	-0.0018	0.0318	0.085	-0.0109	-0.0112	0.1122	0.0244	0.0206	2.6734	-6.7405	12.1455
10	2.2683	2.7535	-0.8904	5.4018	-3.826	4.01	-0.0824	0.059	-0.1745	-0.0938	0.3414	0.0373	0.0298	-0.3912	-0.2589	0.0635	-0.0326	0.0193	0.0996	-0.0041	0.0603	-24.0689	-12.8516	-1.4005
11	8.4601	3.8435	-2.3477	1.7904	-0.9167	1.1778	0.0575	0.0032	-0.2299	0.0368	0.0238	-0.1469	-0.0083	0.1055	-0.0813	0.0786	-0.0135	0.0132	0.0894	-0.0028	0.0637	-22.4515	1.0468	-6.6783
12	3.512	-1.4747	1.1124	4.0542	0.3667	0.5547	0.0981	0.3586	-0.2535	-0.2835	0.0552	-0.1768	-0.0255	0.1643	-0.1533	0.1216	-0.0187	0.0293	0.1418	-0.0137	0.0557	-21.2805	-5.7829	-7.2882
13	1.295	0.7125	-0.4064	8.3093	-7.515	6.8471	0.2089	-0.1766	0.099	0.0255	-0.4512	-0.2253	0.0088	0.404	0.2423	0.0797	-0.0374	-0.0158	0.1189	0.0359	0.0524	13.6042	-0.9529	6.1034
14	8.2297	0.7871	3.6466	0.2047	0.5537	2.0374	0.0079	-0.1192	-0.1387	0.0313	0.003	0.0079	0.0565	-0.1075	-0.011	0.0846	0.0038	-0.0035	0.0684	0.0032	0.0679	11.6934	-0.3539	-8.1773
15	3.2063	1.1834	-0.9747	0.9717	-0.0068	0.5306	-0.0019	-0.1528	-0.0391	-0.037	-0.0539	0.0341	-0.0241	0.0535	0.0559	0.1155	-0.0055	-0.0019	0.0586	0.0492	0.0688	10.5982	1.9911	-1.9004
16	4.2386	2.9926	-3.2689	2.692	-1.8451	2.9142	0.212	-0.1279	0.0799	0.233	-0.0734	0.0195	-0.0984	0.1429	-0.1386	0.1014	-0.0026	0.0054	0.0865	-0.0305	0.1021	-14.8646	-5.5758	4.2485
17	1.06	0.5639	1.7498	2.7504	0.0744	3.1927	0.1271	0.0406	-0.0431	0.0012	-0.0298	0.0697	0.211	0.0924	-0.0973	0.108	0.0026	0.0145	0.0478	0.0111	0.0548	4.3337	-9.1804	0.8058
18	7.1512	0.2416	1.9215	0.6193	-0.7899	1.7126	-0.0739	0.126	0.0377	0.0397	0.0771	0.0096	-0.0696	-0.07	-0.0032	0.107	0.0055	-0.0107	0.1077	0.0019	0.0015	-14.2191	-4.4264	-9.9072
19	6.9672	1.0108	0.2239	1.3332	-0.2412	0.0703	0.0583	-0.0835	0.0719	0.056	-0.0762	-0.0629	-0.0088	0.012	0.0179	0.1181	-0.0008	0.0053	0.0296	-0.0039	0.0634	3.4558	4.3427	-3.6863

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	B	1 - 5
4	X-RAY DIFFRACTION	1	B	94 - 99
5	X-RAY DIFFRACTION	2	A	6 - 10
6	X-RAY DIFFRACTION	3	B	6 - 10
7	X-RAY DIFFRACTION	4	A	22 - 32
8	X-RAY DIFFRACTION	5	A	33 - 43
9	X-RAY DIFFRACTION	6	B	22 - 32
10	X-RAY DIFFRACTION	7	B	33 - 43
11	X-RAY DIFFRACTION	8	A	44 - 49
12	X-RAY DIFFRACTION	8	A	52 - 56
13	X-RAY DIFFRACTION	9	B	44 - 49
14	X-RAY DIFFRACTION	9	B	52 - 56
15	X-RAY DIFFRACTION	10	A	57 - 62
16	X-RAY DIFFRACTION	11	A	63 - 68
17	X-RAY DIFFRACTION	12	A	69 - 76
18	X-RAY DIFFRACTION	13	B	57 - 62
19	X-RAY DIFFRACTION	14	B	63 - 68
20	X-RAY DIFFRACTION	15	B	69 - 76
21	X-RAY DIFFRACTION	16	A	77 - 85
22	X-RAY DIFFRACTION	17	B	77 - 85
23	X-RAY DIFFRACTION	18	A	86 - 93
24	X-RAY DIFFRACTION	19	B	86 - 93

-
News

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

New format data for meta-information of EMDB entries

Version 3 of the EMDB header file is now the official format.
The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi

Thousand views of thousand structures

Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

-
Movie

-
Structure viewers

+
Viewer log

-
This page

-
This web site

-
Options

+
Open data

-
Basic information

-
Structure visualization

-
Downloads & links

-
Download

-
Validation report

-
Related structure data

-
Links

-
Assembly

-
Components

-
Experimental details

-
Experiment

-
Sample preparation

-
Data collection

-
Phasing

-
Processing

+
About Yorodumi

-
News

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

-
Aug 12, 2020. Covid-19 info

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi

-Movie

-Structure viewers

+Viewer log

-This page

-This web site

-Options

+Open data

-Basic information

-Structure visualization

-Downloads & links

-Download

-Validation report

-Related structure data

-Links

-Assembly

-Components

-Experimental details

-Experiment

-Sample preparation

-Data collection

-Phasing

-Processing

+About Yorodumi

-News

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

-Aug 12, 2020. Covid-19 info

+Mar 5, 2020. Novel coronavirus structure data

+Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+Jul 12, 2017. Major update of PDB

-Yorodumi

-
Movie

-
Structure viewers

+
Viewer log

-
This page

-
This web site

-
Options

+
Open data

-
Basic information

-
Structure visualization

-
Downloads & links

-
Download

-
Validation report

-
Related structure data

-
Links

-
Assembly

-
Components

-
Experimental details

-
Experiment

-
Sample preparation

-
Data collection

-
Phasing

-
Processing

+
About Yorodumi

-
News

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

-
Aug 12, 2020. Covid-19 info

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi