PDB-4djp: Crystal Structure of wild-type HIV-1 Protease in Complex with MKP73

ID or keywords:

Entry

Database: PDB / ID: 4djp

Title

Crystal Structure of wild-type HIV-1 Protease in Complex with MKP73

Components

Pol polyprotein

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

viral genome integration into host DNA / establishment of integrated proviral latency / RNA stem-loop binding / RNA-directed DNA polymerase activity / endonuclease activity / aspartic-type endopeptidase activity / proteolysis / DNA binding
Similarity search - Function

Biological species

Human immunodeficiency virus 1

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.4 Å

Authors

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

Citation

Journal: J.Med.Chem. / Year: 2012
Title: Design, synthesis, and biological and structural evaluations of novel HIV-1 protease inhibitors to combat drug resistance.
Authors: Parai, M.K. / Huggins, D.J. / Cao, H. / Nalam, M.N. / Ali, A. / Schiffer, C.A. / Tidor, B. / Rana, T.M.

History

Deposition	Feb 2, 2012	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Aug 1, 2012	Provider: repository / Type: Initial release
Revision 1.1	Jan 2, 2013	Group: Database references
Revision 1.2	Nov 15, 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	Feb 28, 2024	Group: Data collection / Database references / Derived calculations Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / 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	4djp.cif.gz	101.6 KB	Display	PDBx/mmCIF format
PDB format	pdb4djp.ent.gz	79.9 KB	Display	PDB format
PDBx/mmJSON format	4djp.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	4djp_validation.pdf.gz	750.4 KB	Display	wwPDB validaton report
Full document	4djp_full_validation.pdf.gz	751.7 KB	Display
Data in XML	4djp_validation.xml.gz	12.3 KB	Display
Data in CIF	4djp_validation.cif.gz	17.4 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/dj/4djp ftp://data.pdbj.org/pub/pdb/validation_reports/dj/4djp	HTTPS FTP

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Related structure data

Related structure data	4djoC 4djqC 4djrC C: citing same article (ref.)
Similar structure data	6oxz-d 6oxt-d 1mer-d 4mc1-d 1lzq-d 6oxy-d 3saa-d 3sa4-d 4djr-d 1mrw-d 4njt-1 6oy0-d 4dqc-d 2qi1-d 2fgu-d 2qhy-d 3em3-d 2aid-d 2i4d-d 1t7j-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: Pol polyprotein

B: Pol polyprotein

hetero molecules

22.4 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)	50.826, 57.967, 61.995
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	19
Space group name H-M	P2₁2₁2₁

#1: Protein	Pol polyprotein / HIV-1 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: SF2 / Gene: gag-pol, pol / Plasmid: pXC35 / Production host: Escherichia coli (E. coli) / Strain (production host): TAP56 / References: UniProt: Q90K99
#2: Chemical	ChemComp-M73 / methyl (2S)-3-({[(2S,3R)-3-hydroxy-4-{[(4-methoxyphenyl)sulfonyl][(2S)-2-methylbutyl]amino}-1-phenylbutan-2-yl]carbamoyl}oxy)-2-methylpropanoate Mass: 564.691 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂₈H₄₀N₂O₈S
#3: Chemical	ChemComp-PO4 / PHOSPHATE ION Mass: 94.971 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: PO₄
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 197 / 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: 41.73 %
Crystal grow	Temperature: 295 K / Method: vapor diffusion, hanging drop / pH: 6.2 Details: 126mM Phosphate buffer, 63mM Sodium Citrate, 24-29% Ammonium Sulfate, pH 6.2, VAPOR DIFFUSION, HANGING DROP, temperature 295K

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Data collection

Diffraction

Mean temperature: 100 K

Diffraction source

Source:

SYNCHROTRON / Site:

APS

/ Beamline: 14-BM-C / Wavelength: 0.9 Å

Detector

Type: ADSC QUANTUM 315 / Detector: CCD / Date: Jul 15, 2010

Radiation

Protocol: SINGLE WAVELENGTH / Scattering type: x-ray

Radiation wavelength

Wavelength: 0.9 Å / Relative weight: 1

Reflection

Resolution: 1.4→50 Å / Num. obs: 36681 / % possible obs: 99.6 % / Redundancy: 6.9 % / R_merge(I) obs: 0.059 / Χ²: 1.118 / Net I/σ(I): 12.7

Reflection shell

Resolution (Å)	Redundancy (%)	R_merge(I) obs	Num. unique all	Χ²	Diffraction-ID	% possible all
1.4-1.45	7	0.32	3641	1.198	1	100
1.45-1.51	7	0.257	3603	1.222	1	100
1.51-1.58	7	0.191	3633	1.207	1	100
1.58-1.66	7	0.157	3627	1.191	1	100
1.66-1.76	7	0.12	3655	1.153	1	100
1.76-1.9	7	0.092	3648	1.095	1	100
1.9-2.09	6.9	0.071	3666	1.002	1	99.9
2.09-2.39	6.8	0.067	3698	1.03	1	100
2.39-3.02	6.7	0.053	3729	1.029	1	99.9
3.02-50	6.4	0.037	3781	1.037	1	96.6

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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 / Resolution: 1.4→39.31 Å / Cor.coef. F_o:F_c: 0.966 / Cor.coef. F_o:F_c free: 0.96 / WR_factor R_free: 0.2085 / WR_factor R_work: 0.1879 / Occupancy max: 1 / Occupancy min: 0.5 / FOM work R set: 0.8875 / SU B: 1.952 / SU ML: 0.04 / SU R Cruickshank DPI: 0.0636 / SU R_free: 0.0618 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.064 / ESU R Free: 0.062 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.1891	1823	5 %	RANDOM
R_work	0.173	-	-	-
obs	0.1738	36518	99.33 %	-

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: 59.86 Å² / B_iso mean: 18.8324 Å² / B_iso min: 7.19 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-0.9 Å²	0 Å²	0 Å²
2-	-	0.28 Å²	0 Å²
3-	-	-	0.62 Å²

Refinement step

Cycle: LAST / Resolution: 1.4→39.31 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1506	0	49	197	1752

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.009	0.022	1657
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.02	1122
X-RAY DIFFRACTION	r_angle_refined_deg	1.296	2.017	2265
X-RAY DIFFRACTION	r_angle_other_deg	0.79	3	2770
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.014	5	212
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	39.659	24.828	58
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	10.265	15	287
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	18.047	15	9
X-RAY DIFFRACTION	r_chiral_restr	0.084	0.2	265
X-RAY DIFFRACTION	r_gen_planes_refined	0.007	0.021	1820
X-RAY DIFFRACTION	r_gen_planes_other	0.002	0.02	298
X-RAY DIFFRACTION	r_mcbond_it	0.551	1.5	1026
X-RAY DIFFRACTION	r_mcbond_other	0.158	1.5	428
X-RAY DIFFRACTION	r_mcangle_it	0.893	2	1681
X-RAY DIFFRACTION	r_scbond_it	1.567	3	631
X-RAY DIFFRACTION	r_scangle_it	2.293	4.5	584

LS refinement shell

Resolution: 1.4→1.436 Å / Total num. of bins used: 20

	R_factor	Num. reflection	% reflection
R_free	0.244	120	-
R_work	0.207	2543	-
all	-	2663	-
obs	-	-	99.29 %

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	2.6145	-0.2737	0.2895	3.9745	-0.664	3.1776	-0.0757	-0.2714	0.1031	0.352	0.0499	-0.1073	-0.2101	-0.0099	0.0258	0.1076	0.0299	0.0035	0.1008	-0.0029	0.0312	21.2255	26.455	29.8013
2	2.0362	-0.9478	0.2309	3.6033	0.5926	4.6559	-0.02	-0.0638	-0.2747	0.1873	0.1156	0.2409	0.2649	-0.1293	-0.0956	0.0628	0.0051	0.0117	0.0559	0.0204	0.0672	19.6606	17.263	23.1282
3	5.9923	1.3285	0.801	3.7185	-2.3729	2.007	-0.0347	0.0758	0.0335	0.0208	-0.0909	-0.1529	-0.028	0.0907	0.1255	0.0203	0.008	-0.0021	0.0157	0.0105	0.0117	26.5032	27.2056	18.137
4	7.4738	0.2062	2.4728	3.5027	-1.4734	2.8893	-0.0151	0.0457	-0.1378	0.0124	0.1334	0.311	-0.0593	-0.0753	-0.1183	0.0272	0.0151	0.0081	0.0221	0.0162	0.0376	13.8035	27.7101	19.4153
5	10.6694	-2.5217	-4.7693	6.6404	0.3045	5.314	-0.0452	-0.1702	0.2985	0.2962	-0.2598	-1.2653	-0.2895	0.4738	0.305	0.1132	-0.053	-0.1233	0.1209	0.0853	0.3009	39.5421	31.0247	23.4968
6	16.0642	-5.7288	-3.9333	4.3526	2.8975	4.1352	0.1819	0.3853	-0.6877	-0.2491	-0.1788	0.7542	-0.2287	-0.5816	-0.0031	0.1117	-0.0017	-0.0344	0.1541	0.0374	0.3611	1.3547	22.0052	18.1788
7	4.1414	-0.4756	-0.4377	2.0984	1.9384	4.9484	0.0124	0.2992	0.1873	-0.223	0.1003	-0.4351	-0.1211	0.6659	-0.1127	0.1172	-0.0159	0.0192	0.1932	0.0597	0.1598	39.7408	31.1362	9.4985
8	6.021	-3.0513	-2.0849	9.0408	4.2645	3.4432	0.115	0.2876	-0.0049	-0.0386	-0.1754	0.6646	0.0025	-0.6922	0.0604	0.1135	0.0095	-0.0084	0.2673	0.0875	0.1237	0.3257	34.4385	13.2277
9	13.0594	-1.9542	-3.4763	2.7466	0.295	4.1658	-0.0369	0.1543	-0.1526	-0.2107	-0.0885	-0.0265	0.0527	0.1129	0.1255	0.0932	0.0083	-0.0061	0.0527	0.0048	0.0205	27.4957	30.5846	4.3699
10	12.5269	-4.0452	-1.6468	3.2489	-0.8848	1.4221	0.0428	0.0813	-0.0172	0.0114	0.0286	0.1842	-0.0881	-0.0366	-0.0715	0.0678	-0.0019	0.0013	0.0322	0.0097	0.0441	12.4303	39.4924	11.3323
11	1.0167	0.6385	-0.5423	3.5182	-2.349	6.1232	0.0043	-0.0183	0.1592	-0.0139	-0.0508	0.1681	-0.254	0.0117	0.0465	0.0333	-0.0073	-0.0227	0.021	0.0119	0.049	29.0967	33.5463	14.3543
12	5.5099	-3.8974	5.4284	3.7928	-4.0094	5.3958	0.2847	0.2632	-0.1876	-0.3338	-0.0542	0.2726	0.3297	0.202	-0.2305	0.0765	-0.0235	-0.0348	0.0975	0.0315	0.0584	10.4399	29.3137	12.157
13	7.3209	-2.0955	1.7254	2.671	-2.408	3.8633	0.0097	0.0698	-0.28	-0.0092	-0.0324	-0.0731	0.304	0.0449	0.0228	0.0554	0.0092	-0.0044	0.0191	0.0046	0.0302	28.685	19.1715	19.3926
14	14.1443	-6.2534	-1.0905	6.0275	-1.3048	2.6277	-0.6793	-1.0322	0.1207	0.5964	0.7483	0.5743	-0.0017	-0.0788	-0.069	0.0937	0.0915	0.0671	0.1143	0.0448	0.1722	11.9484	29.1066	27.3962
15	0.5706	-1.9169	0.6873	8.0811	-7.3095	16.2611	0.1156	0.1266	-0.0298	-0.4441	-0.4573	-0.0634	0.5214	0.3785	0.3417	0.0688	0.0819	0.0649	0.185	0.0674	0.2153	38.8056	22.6384	10.2833
16	9.592	7.8792	-10.8626	13.576	-12.233	13.8575	0.2563	-0.3256	0.2542	0.6414	0.0914	0.4577	-0.4836	0.1854	-0.3477	0.0662	0.0495	0.0415	0.1338	0.0091	0.2264	1.5367	36.7878	21.4216
17	12.6025	-1.9639	-8.5935	6.9744	1.6054	22.9981	-0.1122	-0.0272	0.3491	0.4033	-0.0759	-0.4097	-0.1394	0.5103	0.1882	0.0742	-0.0366	-0.0695	0.0436	0.0413	0.1503	37.8228	23.8584	24.101
18	17.0399	-13.8774	6.9315	15.3747	-4.0548	4.225	0.2102	0.6602	-0.5306	0.1638	-0.6106	0.5446	0.5096	0.2369	0.4004	0.2483	0.0623	0.2017	0.1586	0.0041	0.4057	3.0614	23.2137	24.8805
19	1.9719	-1.2192	-0.0271	3.9629	-1.5249	5.835	0.013	-0.0633	0.015	0.1792	-0.1826	-0.3111	0.2405	0.3024	0.1696	0.0414	0.0033	0.0081	0.0638	0.0351	0.0934	36.63	21.1637	19.8352
20	1.3423	2.2035	-3.0749	7.5327	-6.3616	8.9023	-0.1124	-0.1862	-0.0478	0.0851	0.0953	0.2706	0.3022	0.0789	0.0171	0.0865	0.0522	0.0407	0.1172	0.049	0.1286	4.3289	28.728	25.7235

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 - 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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