PDB-3sa3: Crystal structure of wild-type HIV-1 protease in complex with AG23

ID or keywords:

Entry

Database: PDB / ID: 3sa3

Title

Crystal structure of wild-type HIV-1 protease in complex with AG23

Components

Protease

Keywords

HYDROLASE/HYDROLASE INHIBITOR / HIV-1 protease / drug resistance / drug design / protease inhibitors / AIDS / aspartyl protease / HYDROLASE-HYDROLASE INHIBITOR complex

Function / homology

Function and homology information

aspartic-type endopeptidase activity / proteolysis
Similarity search - Function

Biological species

Human immunodeficiency virus 1

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.65 Å

Authors

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

Citation

Journal: To be Published
Title: Protease Inhibitors that protrude out from substrate envelope are more susceptible to developing drug resistance
Authors: Altman, M.D. / Nalam, M.N.L. / Ali, A. / Cao, H. / Rana, T.M. / Schiffer, C.A. / Tidor, B.

History

Deposition	Jun 2, 2011	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Jun 6, 2012	Provider: repository / Type: Initial release
Revision 1.1	Dec 12, 2012	Group: Other
Revision 1.2	Nov 8, 2017	Group: Refinement description / Category: software Item: _software.classification / _software.contact_author ..._software.classification / _software.contact_author / _software.contact_author_email / _software.date / _software.language / _software.location / _software.name / _software.type / _software.version
Revision 1.3	Sep 13, 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

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Download

PDBx/mmCIF format	3sa3.cif.gz	95.5 KB	Display	PDBx/mmCIF format
PDB format	pdb3sa3.ent.gz	74.4 KB	Display	PDB format
PDBx/mmJSON format	3sa3.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	3sa3_validation.pdf.gz	798.6 KB	Display	wwPDB validaton report
Full document	3sa3_full_validation.pdf.gz	799.6 KB	Display
Data in XML	3sa3_validation.xml.gz	11.3 KB	Display
Data in CIF	3sa3_validation.cif.gz	15.5 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/sa/3sa3 ftp://data.pdbj.org/pub/pdb/validation_reports/sa/3sa3	HTTPS FTP

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Related structure data

Related structure data	3sa4C 3sa5C 3sa6C 3sa7C 3sa8C 3sa9C 3saaC 3sabC 3sacC 1f7aS C: citing same article (ref.) S: Starting model for refinement
Similar structure data	4dqc-d 3o9f-d 6oxx-d 2z54-d 3oxx-2 2psu-d 1g2k-d 1n49-1 4u7v-d 4djp-d 6oy2-d 6oxw-d 3gi4-d 3em3-d 4mc6-d 6oxr-d 3sa8-d 6pjc-2 6oxt-d 3nu6-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)

Deposited unit

A: Protease

B: 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)	50.386, 57.330, 61.097
Angle α, β, γ (deg.)	90.00, 90.00, 90.00
Int Tables number	19
Space group name H-M	P2₁2₁2₁

#1: Protein	Protease Mass: 10815.790 Da / Num. of mol.: 2 / Mutation: Q7K 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: O38732
#2: Chemical	ChemComp-ACT / ACETATE ION Mass: 59.044 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₂H₃O₂
#3: Chemical	ChemComp-PO4 / PHOSPHATE ION Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO₄
#4: Chemical	ChemComp-23X / N~2~-acetyl-N-[(2S,3R)-4-{(1,3-benzothiazol-6-ylsulfonyl)[(2S)-2-methylbutyl]amino}-3-hydroxy-1-phenylbutan-2-yl]-L-isoleucinamide Type: Peptide-like / Class: Inhibitor / Mass: 602.808 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₃₀H₄₂N₄O₅S₂ References: N~2~-ACETYL-N-[(2S,3R)-4-{(1,3-BENZOTHIAZOL-6-YLSULFONYL)[(2S)-2-METHYLBUTYL]AMINO}-3-HYDROXY-1-PHENYLBUTAN-2-YL]-L-ISOLEUCINAMIDE
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 126 / 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: 2.04 Å³/Da / Density % sol: 39.7 %
Crystal grow	Temperature: 295 K / Method: hanging drop, vapor diffusion / pH: 6.2 Details: 24-29% ammonium sulfate, 63 mM sodium citrate, 126 mM phosphate buffer, pH 6.2, HANGING DROP, VAPOR DIFFUSION, temperature 295K

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Data collection

Diffraction

Mean temperature: 100 K

Diffraction source

Source:

SYNCHROTRON / Site:

NSLS

/ Beamline: X29A / Wavelength: 1.075

Detector

Type: ADSC QUANTUM 315 / Detector: CCD / Date: Jan 20, 2010

Radiation

Protocol: SINGLE WAVELENGTH / Scattering type: x-ray

Radiation wavelength

Wavelength: 1.075 Å / Relative weight: 1

Reflection

Resolution: 1.65→50 Å / Num. obs: 21177 / % possible obs: 96.5 % / Redundancy: 4.9 % / R_merge(I) obs: 0.057 / Χ²: 1.034 / Net I/σ(I): 13.2

Reflection shell

Resolution (Å)	Redundancy (%)	R_merge(I) obs	Num. unique all	Χ²	Diffraction-ID	% possible all
1.65-1.71	4.8	0.356	2089	0.812	1	97.2
1.71-1.78	4.9	0.259	2107	0.882	1	98
1.78-1.86	4.9	0.205	2109	1.03	1	97.8
1.86-1.96	4.9	0.149	2141	1.054	1	98.5
1.96-2.08	4.9	0.113	2123	1.172	1	97.8
2.08-2.24	4.9	0.093	2116	1.178	1	97.7
2.24-2.46	4.9	0.077	2139	1.062	1	97.3
2.46-2.82	4.9	0.064	2118	0.976	1	96.1
2.82-3.55	4.9	0.057	2111	1.069	1	95
3.55-50	4.8	0.035	2124	1.094	1	89.8

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Processing

Software

Name	Version	Classification
DENZO		data reduction
SCALEPACK		data scaling
REFMAC		refinement
PDB_EXTRACT	3.1	data extraction
HKL-2000		data collection
HKL-2000		data reduction
AMoRE		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1F7A

1f7a

Resolution: 1.65→41.81 Å / Cor.coef. F_o:F_c: 0.966 / Cor.coef. F_o:F_c free: 0.956 / WR_factor R_free: 0.2175 / WR_factor R_work: 0.1885 / Occupancy max: 1 / Occupancy min: 0.5 / FOM work R set: 0.8773 / SU B: 3.836 / SU ML: 0.065 / SU R Cruickshank DPI: 0.1059 / SU R_free: 0.1011 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.106 / ESU R Free: 0.101 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : RESIDUAL ONLY

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.203	1080	5.1 %	RANDOM
R_work	0.1722	-	-	-
obs	0.1737	21153	96.56 %	-

Solvent computation

Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK

Displacement parameters

B_iso max: 59.08 Å² / B_iso mean: 25.181 Å² / B_iso min: 2 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-1.09 Å²	0 Å²	0 Å²
2-	-	-0.3 Å²	0 Å²
3-	-	-	1.39 Å²

Refinement step

Cycle: LAST / Resolution: 1.65→41.81 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1494	0	58	126	1678

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.009	0.022	1631
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.02	1085
X-RAY DIFFRACTION	r_angle_refined_deg	1.434	2.019	2228
X-RAY DIFFRACTION	r_angle_other_deg	0.826	3	2681
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.584	5	208
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	41.586	24.909	55
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	12.829	15	272
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	14.748	15	8
X-RAY DIFFRACTION	r_chiral_restr	0.087	0.2	264
X-RAY DIFFRACTION	r_gen_planes_refined	0.006	0.021	1795
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	293
X-RAY DIFFRACTION	r_mcbond_it	0.609	1.5	1023
X-RAY DIFFRACTION	r_mcbond_other	0.16	1.5	424
X-RAY DIFFRACTION	r_mcangle_it	1.065	2	1661
X-RAY DIFFRACTION	r_scbond_it	1.846	3	608
X-RAY DIFFRACTION	r_scangle_it	2.732	4.5	567

LS refinement shell

Resolution: 1.65→1.693 Å / Total num. of bins used: 20

	R_factor	Num. reflection	% reflection
R_free	0.254	86	-
R_work	0.195	1443	-
all	-	1529	-
obs	-	-	96.53 %

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	2.6579	-0.5215	0.0776	2.9956	0.0847	2.4778	-0.1451	-0.3119	0.0638	0.2809	0.1519	0.044	-0.1328	0.0175	-0.0068	0.1113	0.043	0.018	0.0993	-0.0045	0.0063	20.9319	25.8662	29.2866
2	3.0059	-1.9082	-0.4972	2.041	0.1866	2.6098	-0.1168	-0.0088	-0.2719	0.1718	0.1087	0.2711	0.2285	-0.0685	0.0081	0.1029	-0.0012	0.0216	0.0539	0.0239	0.0627	19.7155	17.2077	22.8816
3	3.4846	1.2086	1.3902	2.5279	-0.3529	1.4243	-0.0425	0.0458	0.0759	0.0641	-0.0419	-0.0618	-0.1328	0.0266	0.0844	0.11	0.0107	-0.0099	0.0743	0.0052	0.0471	27.7464	27.85	18.2639
4	3.3603	0.562	1.0669	3.7103	0.039	1.246	0.0344	-0.0162	-0.1092	-0.0161	0.1302	0.1666	-0.0372	-0.0288	-0.1646	0.0813	0.0138	0.0056	0.0694	0.0323	0.0718	12.4332	26.8107	18.5473
5	12.1569	0.8872	-3.7989	6.5747	0.0206	6.7573	-0.0881	-0.353	-0.1995	0.3354	-0.2702	-1.0525	-0.3052	0.4928	0.3583	0.0916	-0.0289	-0.1164	0.0918	0.0781	0.2349	39.4719	30.1865	23.5641
6	6.2674	-3.007	-8.2647	7.5762	5.5472	11.3388	0.2197	0.5128	-0.1206	-0.1393	-0.5963	1.3291	-0.3946	-0.825	0.3766	0.1371	0.0406	0.0281	0.2901	0.0142	0.4749	1.0787	21.3654	18.5344
7	7.2584	-1.4542	-1.0312	3.7611	2.3991	6.9411	0.0357	0.289	0.2817	-0.078	-0.0381	-0.3423	-0.0854	0.4417	0.0024	0.036	-0.0152	0.0063	0.1354	0.0817	0.0881	38.9033	30.2037	9.3346
8	6.8067	-3.6139	-0.6674	9.2245	2.3892	4.4967	0.3035	0.4235	-0.1759	0.0336	-0.247	0.4255	0.1523	-0.5701	-0.0566	0.0398	0.0083	0.0121	0.165	0.0588	0.0693	0.3848	33.705	13.0554
9	10.0771	-0.9182	-1.9209	2.377	-1.3351	3.937	-0.0702	0.2388	0.0077	-0.0311	0.066	0.0062	-0.0228	0.0309	0.0042	0.1001	0.0049	0.0084	0.0673	-0.0109	0.0155	26.9287	30.3986	4.3123
10	6.7296	-0.6561	-1.5987	4.5119	-3.269	3.0197	-0.0013	0.1434	-0.1263	-0.1457	0.043	0.1167	0.1012	-0.0802	-0.0417	0.0869	0.0137	-0.0056	0.062	-0.0136	0.0455	12.2296	39.0603	11.1845
11	1.3107	1.5375	-1.457	2.3396	-0.6568	5.14	0.037	0.036	0.111	0.0268	-0.0609	0.1446	-0.2719	0.0534	0.0239	0.1043	-0.0064	-0.0203	0.0903	0.0184	0.0887	29.062	33.0479	13.9667
12	3.7641	-2.8902	1.9593	3.909	-0.3288	2.6932	0.1682	0.2631	-0.0902	-0.2115	-0.135	0.1781	0.2112	0.1617	-0.0331	0.0667	0.0014	-0.018	0.0867	0.0248	0.0586	10.443	28.8233	11.9872
13	0.849	-1.6083	0.1513	3.2193	-0.8195	1.8154	-0.01	0.0003	-0.0055	0.0363	-0.0169	-0.0259	-0.0312	-0.0355	0.0269	0.0999	0.0033	-0.0197	0.1	0.0134	0.0871	28.5378	18.8884	19.1946
14	4.6402	-3.5967	0.3221	3.1985	-1.5322	4.0468	-0.2703	-0.4869	-0.2817	0.2504	0.4196	0.2711	-0.1343	-0.1165	-0.1494	0.1294	0.0493	0.0488	0.1394	0.0553	0.0995	12.0425	29.0916	27.2243
15	1.3577	-4.8731	4.0808	17.5562	-14.1401	19.4633	0.1565	0.1176	0.1	-0.5374	-0.4178	-0.4361	0.3187	0.2559	0.2614	0.0449	0.0449	0.0563	0.1366	0.0318	0.1949	38.6701	22.3378	10.2208
16	4.903	4.0275	-6.8105	8.4515	-8.0873	16.8573	0.132	-0.1112	0.2653	0.4123	0.0526	0.341	-0.5296	0.0834	-0.1846	0.0501	0.0417	0.0435	0.0666	0.0503	0.136	1.7184	36.3437	21.2501
17	19.6688	1.3187	-10.387	7.646	-4.3895	15.4101	0.1295	-0.1313	1.0707	0.5153	0.0896	-0.4321	-0.3833	-0.02	-0.219	0.1144	-0.0281	-0.122	0.0576	0.0019	0.2211	37.4984	23.8014	23.9613
18	38.0366	-7.4734	5.7327	1.5008	-0.9599	1.7387	0.1511	1.3312	-1.1223	0.0222	-0.1548	0.2405	0.2445	0.6724	0.0037	0.3487	0.0471	0.1902	0.3223	-0.0023	0.3881	3.1663	22.819	24.8763
19	1.3791	-1.6439	2.2075	3.4428	-1.8441	5.9438	0.003	0.0898	0.0041	0.003	-0.0947	-0.3429	0.0093	-0.067	0.0917	0.0473	-0.0037	0.006	0.0857	0.0016	0.1317	35.4983	21.2111	18.3579
20	2.5149	2.7303	-4.2325	2.985	-4.6554	7.8817	-0.1992	-0.1595	-0.0921	-0.2263	-0.1483	-0.0564	0.3858	0.2202	0.3474	0.1433	0.0583	0.058	0.1183	0.0828	0.2825	4.2771	28.5492	25.5783

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	20 - 32
8	X-RAY DIFFRACTION	4	B	20 - 32
9	X-RAY DIFFRACTION	5	A	11 - 19
10	X-RAY DIFFRACTION	6	B	11 - 19
11	X-RAY DIFFRACTION	7	A	33 - 43
12	X-RAY DIFFRACTION	8	B	33 - 43
13	X-RAY DIFFRACTION	9	A	44 - 57
14	X-RAY DIFFRACTION	10	B	44 - 57
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	58 - 62
20	X-RAY DIFFRACTION	16	B	58 - 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

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