PDB-3sa4: Crystal structure of wild-type HIV-1 protease in complex with AF72

ID or keywords:

Entry

Database: PDB / ID: 3sa4

Title

Crystal structure of wild-type HIV-1 protease in complex with AF72

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 /

MOLECULAR REPLACEMENT / Resolution: 1.8 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
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	3sa4.cif.gz	96.7 KB	Display	PDBx/mmCIF format
PDB format	pdb3sa4.ent.gz	75.2 KB	Display	PDB format
PDBx/mmJSON format	3sa4.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	3sa4_validation.pdf.gz	803 KB	Display	wwPDB validaton report
Full document	3sa4_full_validation.pdf.gz	804.6 KB	Display
Data in XML	3sa4_validation.xml.gz	11.6 KB	Display
Data in CIF	3sa4_validation.cif.gz	15.6 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/sa/3sa4 ftp://data.pdbj.org/pub/pdb/validation_reports/sa/3sa4	HTTPS FTP

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Related structure data

Related structure data	3sa3C 3sa5C 3sa6C 3sa7C 3sa8C 3sa9C 3saaC 3sabC 3sacC 1f7aS C: citing same article (ref.) S: Starting model for refinement
Similar structure data	4u7v-d 3saa-d 1zpa-1 2zga-1 2qhc-d 4djp-d 6oot-d 6mcr-1 3oxv-2 3em3-d 1lzq-d 1t7i-d 6oxv-d 5kr1-d 4ep2-d 2r43-d 1bwa-d 3tlh-1 3ekt-1 1f7a-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)	50.893, 58.004, 61.742
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
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-PO4 / PHOSPHATE ION Mass: 94.971 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: PO₄
#3: Chemical	ChemComp-ACT / ACETATE ION Mass: 59.044 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂H₃O₂
#4: Chemical	ChemComp-F72 / N-{(2S,3R)-4-[(1,3-benzothiazol-6-ylsulfonyl)(cyclohexylmethyl)amino]-3-hydroxy-1-phenylbutan-2-yl}-3-hydroxybenzamide Type: Peptide-like / Class: Inhibitor / Mass: 593.757 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₃₁H₃₅N₃O₅S₂ References: N-{(2S,3R)-4-[(1,3-BENZOTHIAZOL-6-YLSULFONYL)(CYCLOHEXYLMETHYL)AMINO]-3-HYDROXY-1-PHENYLBUTAN-2-YL}-3-HYDROXYBENZAMIDE
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 127 / 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: 2.11 Å³/Da / Density % sol: 41.61 %
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:

ROTATING ANODE / Type: RIGAKU / Wavelength: 1.5418

Detector

Type: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Jun 12, 2009

Radiation

Protocol: SINGLE WAVELENGTH / Scattering type: x-ray

Radiation wavelength

Wavelength: 1.5418 Å / Relative weight: 1

Reflection

Resolution: 1.8→50 Å / Num. obs: 16543 / % possible obs: 94.2 % / Redundancy: 7 % / R_merge(I) obs: 0.054 / Χ²: 0.957 / Net I/σ(I): 13.2

Reflection shell

Resolution (Å)	Redundancy (%)	R_merge(I) obs	Num. unique all	Χ²	Diffraction-ID	% possible all
1.8-1.86	5.6	0.383	1344	0.859	1	77.9
1.86-1.94	7.1	0.255	1603	0.858	1	93.4
1.94-2.03	7.2	0.173	1628	0.892	1	94.5
2.03-2.13	7.2	0.128	1635	0.939	1	94.6
2.13-2.27	7.2	0.103	1640	0.974	1	95.1
2.27-2.44	7.2	0.088	1668	1.025	1	96
2.44-2.69	7.2	0.066	1694	1.046	1	96.7
2.69-3.08	7.2	0.047	1720	1.027	1	96.9
3.08-3.88	7	0.034	1748	0.952	1	98.1
3.88-50	6.8	0.03	1863	0.947	1	98.4

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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 reduction
HKL-2000		data scaling
AMoRE		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1F7A

1f7a

Resolution: 1.8→42.27 Å / Cor.coef. F_o:F_c: 0.959 / Cor.coef. F_o:F_c free: 0.945 / WR_factor R_free: 0.2042 / WR_factor R_work: 0.169 / Occupancy max: 1 / Occupancy min: 0.5 / FOM work R set: 0.8651 / SU B: 5.675 / SU ML: 0.083 / SU R Cruickshank DPI: 0.1476 / SU R_free: 0.1327 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.148 / ESU R Free: 0.133 / 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	0.2128	829	5 %	RANDOM
R_work	0.1762	-	-	-
obs	0.178	16511	94.29 %	-

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: 48.61 Å² / B_iso mean: 26.397 Å² / B_iso min: 13.65 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-0.45 Å²	0 Å²	0 Å²
2-	-	0.12 Å²	0 Å²
3-	-	-	0.32 Å²

Refinement step

Cycle: LAST / Resolution: 1.8→42.27 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1494	0	59	127	1680

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.008	0.022	1658
X-RAY DIFFRACTION	r_bond_other_d	0.006	0.02	1110
X-RAY DIFFRACTION	r_angle_refined_deg	1.366	2.023	2270
X-RAY DIFFRACTION	r_angle_other_deg	0.842	3	2737
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.232	5	212
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	43.489	24.915	59
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	12.294	15	276
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	17.29	15	9
X-RAY DIFFRACTION	r_chiral_restr	0.078	0.2	263
X-RAY DIFFRACTION	r_gen_planes_refined	0.006	0.021	1838
X-RAY DIFFRACTION	r_gen_planes_other	0.002	0.02	302
X-RAY DIFFRACTION	r_mcbond_it	0.547	1.5	1032
X-RAY DIFFRACTION	r_mcbond_other	0.153	1.5	428
X-RAY DIFFRACTION	r_mcangle_it	0.931	2	1681
X-RAY DIFFRACTION	r_scbond_it	1.468	3	626
X-RAY DIFFRACTION	r_scangle_it	2.314	4.5	589

LS refinement shell

Resolution: 1.8→1.847 Å / Total num. of bins used: 20

	R_factor	Num. reflection	% reflection
R_free	0.332	50	-
R_work	0.264	864	-
all	-	914	-
obs	-	-	73.06 %

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	2.7632	-0.9674	0.671	2.5018	-0.2087	2.3458	-0.1054	-0.3083	0.0328	0.2683	0.0381	-0.0684	-0.0891	0.0026	0.0674	0.0685	0.0197	0.0001	0.0483	0.0045	0.0059	20.9548	25.9621	29.5839
2	2.2578	-1.4516	0.2549	2.9679	0.4595	2.6582	-0.0768	-0.0104	-0.2863	0.0828	0.1452	0.2468	0.1094	-0.0704	-0.0683	0.0249	0.0058	0.0176	0.0184	0.0125	0.0445	19.7293	17.4148	22.9855
3	2.4177	1.1232	0.8216	1.6666	-0.5026	1.1026	-0.0666	0.0308	-0.0254	-0.013	-0.0392	-0.1072	-0.0741	0.0249	0.1058	0.0183	0.0112	-0.0095	0.0173	-0.0003	0.0211	27.9475	28.405	18.6468
4	4.7639	0.3596	0.7527	3.9098	0.2258	2.2037	0.0263	0.0477	-0.1512	-0.0669	0.0818	0.1771	-0.1028	-0.016	-0.1081	0.0073	0.001	0.0008	0.0031	0.0038	0.0182	12.5217	27.0034	18.5326
5	0.7138	-1.2097	-0.525	2.8878	1.5767	1.001	-0.0748	-0.1826	0.0653	0.0354	0.1302	-0.2638	-0.0894	0.0108	-0.0553	0.1073	0.0002	-0.1058	0.1204	0.0829	0.2541	39.9363	30.4541	24.0591
6	9.796	-3.5837	-1.7787	1.6927	1.3251	1.5172	0.087	-0.0255	-0.3662	-0.0523	-0.1107	0.1126	-0.0547	-0.2002	0.0236	0.0067	-0.0009	-0.0017	0.0469	0.005	0.0608	0.9657	21.6249	18.0801
7	3.905	-0.0282	0.3193	1.2671	2.3987	4.8764	-0.0116	0.1873	-0.0025	-0.03	0.0911	-0.1415	-0.1082	0.3073	-0.0795	0.0209	-0.0267	-0.0213	0.0642	0.0619	0.1368	39.4583	31.7455	10.2512
8	7.1995	-0.6458	-0.8281	7.9264	2.6935	4.9081	0.0791	0.2758	-0.0276	-0.1489	-0.0702	0.4653	0.1485	-0.5574	-0.009	0.0224	-0.0038	-0.0043	0.1202	0.0474	0.0546	0.422	34.2319	13.1853
9	8.7913	-2.3699	-1.3762	1.5738	0.5255	2.4408	-0.0313	0.2725	-0.2112	0.0009	-0.1039	0.0146	-0.0025	0.0287	0.1352	0.0281	0.0078	0.0044	0.0148	-0.0003	0.0128	27.6371	30.6313	4.4996
10	4.7658	-1.9203	-1.1217	3.4158	-1.1381	2.5254	0.1579	0.0286	0.2055	-0.0797	0.0124	0.0827	-0.0951	-0.0882	-0.1702	0.0186	0.0081	0.0046	0.0055	0.003	0.0202	12.4123	39.6394	11.5237
11	2.1129	-0.7055	-0.5353	3.1737	-0.3656	4.0469	0.0286	0.0808	0.1795	-0.0282	0.0004	0.1811	-0.3003	-0.0094	-0.0289	0.0247	-0.0023	-0.0041	0.0068	0.0097	0.036	29.2658	33.4692	14.4606
12	5.2978	-3.9716	4.2187	3.5561	-3.7366	3.9292	0.2732	0.2807	-0.0203	-0.2606	-0.1186	0.1608	0.2765	0.1371	-0.1546	0.0543	0.0059	-0.0135	0.0282	0.0197	0.0434	10.4893	29.4482	12.1192
13	1.9496	0.2494	-0.1818	0.9986	0.5098	0.4291	-0.0405	0.0194	0.0073	0.0541	-0.0154	-0.0125	0.0312	0.0234	0.0558	0.0226	0.0063	-0.0066	0.0193	0.0146	0.0383	28.7617	19.221	19.433
14	4.0623	-3.4504	-1.5666	4.3595	-0.0699	1.9776	-0.1552	-0.3046	-0.1522	0.1352	0.198	0.228	0.0473	0.1681	-0.0428	0.0455	0.055	0.0152	0.074	0.0176	0.0146	11.9168	28.9759	27.2312
15	0.4305	-0.7477	1.9067	4.947	-4.5481	8.8763	0.0137	0.0369	0.0146	-0.2271	-0.1741	-0.2307	0.1259	0.2098	0.1604	0.0157	0.0165	0.0221	0.0314	0.0265	0.0565	38.9397	22.8585	10.4586
16	8.5379	4.0202	-2.3149	8.1405	-3.0849	7.0442	0.306	-0.0382	0.068	0.4494	0.0592	0.271	-0.6131	-0.0186	-0.3653	0.0628	0.016	0.0351	0.0452	0.0248	0.1016	1.6109	36.6839	21.3277
17	4.3382	-1.4614	-2.2671	9.0807	2.3083	6.0424	0.0362	0.0524	0.6141	0.2661	-0.0282	-0.1331	-0.1574	0.0716	-0.0079	0.0232	-0.0082	-0.0133	0.007	0.0194	0.1188	37.8086	24.0778	24.2962
18	8.4678	-1.1628	-1.868	1.4134	2.9579	6.2543	-0.1763	0.1102	-0.0434	0.0981	0.1026	0.0284	0.2124	0.2166	0.0737	0.0197	0.0062	0.0183	0.0299	0.0196	0.0366	2.7521	23.1253	24.4995
19	1.5774	-0.3905	1.1655	2.3382	0.133	2.1375	-0.0528	0.1481	0.0059	0.0599	-0.0816	-0.2321	-0.031	0.2442	0.1344	0.0115	-0.0001	0.0049	0.036	0.0326	0.0604	35.7764	21.5861	18.662
20	1.9074	0.4066	-2.2707	6.1086	-2.1149	3.1457	-0.1035	-0.0354	0.0338	0.0976	0.2379	0.3541	0.0885	-0.0299	-0.1344	0.0115	0.0189	0.0052	0.0553	0.0218	0.0344	4.1656	28.5883	25.6267
21	2.7021	-3.2513	-0.6265	9.3921	3.9266	5.0852	0.0684	-0.1436	0.0922	-0.2747	0.2622	-0.1978	-0.1774	0.2819	-0.3307	0.0456	-0.0045	0.0203	0.0248	-0.0192	0.0312	19.8063	30.8132	14.5464

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
25	X-RAY DIFFRACTION	21	B	200

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