PDB-5qcp: Crystal structure of BACE complex with BMC018

ID or keywords:

Entry

Database: PDB / ID: 5qcp

Title

Crystal structure of BACE complex with BMC018

Components

Beta-secretase 1

Keywords

HYDROLASE / Hydroloase / D3R / BACE / Ligand Docking

Function / homology

Function and homology information

memapsin 2 / Golgi-associated vesicle lumen / beta-aspartyl-peptidase activity / signaling receptor ligand precursor processing / amyloid precursor protein catabolic process / amyloid-beta formation / membrane protein ectodomain proteolysis / amyloid-beta metabolic process / detection of mechanical stimulus involved in sensory perception of pain / prepulse inhibition ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

MOLECULAR REPLACEMENT /

molecular replacement / Resolution: 2.45 Å

Model details

Structures for D3R docking challenge

Authors

Rondeau, J.M. / Shao, C. / Yang, H. / Burley, S.K.

Citation

Journal: J.Comput.Aided Mol.Des. / Year: 2020
Title: D3R grand challenge 4: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies.
Authors: Parks, C.D. / Gaieb, Z. / Chiu, M. / Yang, H. / Shao, C. / Walters, W.P. / Jansen, J.M. / McGaughey, G. / Lewis, R.A. / Bembenek, S.D. / Ameriks, M.K. / Mirzadegan, T. / Burley, S.K. / Amaro, R.E. / Gilson, M.K.

History

Deposition	Dec 1, 2017	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Jun 3, 2020	Provider: repository / Type: Initial release
Revision 1.1	Dec 30, 2020	Group: Structure summary / Category: audit_author / Item: _audit_author.identifier_ORCID
Revision 1.2	Feb 10, 2021	Group: Database references / Category: citation_author / Item: _citation_author.identifier_ORCID
Revision 1.3	Nov 20, 2024	Group: Data collection / Database references / Structure summary Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	5qcp.cif.gz	460.2 KB	Display	PDBx/mmCIF format
PDB format	pdb5qcp.ent.gz	380.7 KB	Display	PDB format
PDBx/mmJSON format	5qcp.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/qc/5qcp ftp://data.pdbj.org/pub/pdb/validation_reports/qc/5qcp	HTTPS FTP

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Group deposition

ID	G_1002044 (26 entries) 5qco 5qcp 5qcq 5qcr 5qcs 5qct 5qcu 5qcv 5qcw 5qcx
Title	Crystal Structures of Beta-Secretase 1 with Bound Ligands
Type	undefined
Description	Crystal Structures of Complexes of Beta-Secretase 1 and Ligands

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Related structure data

Similar structure data	5qd9-3 3dv1-1 5qd1-1 3k5g-1 4b1d-d 5qcy-2 3i25-2 5qcw-3 3duy-1 5qcx-2 2f3e-2 3r2f-2 5qct-1 4gmi-d 6nv9-1 2f3f-1 3skg-3 6dhc-3 4gid-4 5qcu-2 Search similar-shape structures by Omokage search (details) 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

Similar structure data

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Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#115 - Jul 2009 beta-Secretase similarity (5) #79 - Jul 2006 Amyloid-beta Precursor Protein similarity (5)

Deposited unit

A: Beta-secretase 1

B: Beta-secretase 1

C: Beta-secretase 1

hetero molecules

136 kDa, 3 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: Beta-secretase 1

hetero molecules

defined by author
45.4 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Beta-secretase 1

hetero molecules

defined by author
45.4 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

3

C: Beta-secretase 1

hetero molecules

defined by author
45.4 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	82.014, 103.364, 100.120
Angle α, β, γ (deg.)	90.00, 103.70, 90.00
Int Tables number	4
Space group name H-M	P12₁1

#1: Protein	Beta-secretase 1 / Aspartyl protease 2 / Asp 2 / Beta-site amyloid precursor protein cleaving enzyme 1 / Beta-site APP ...Aspartyl protease 2 / Asp 2 / Beta-site amyloid precursor protein cleaving enzyme 1 / Beta-site APP cleaving enzyme 1 / Memapsin-2 / Membrane-associated aspartic protease 2 Mass: 44777.336 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BACE1, BACE, KIAA1149 / Production host: Escherichia coli (E. coli) / References: UniProt: P56817, memapsin 2
#2: Chemical	ChemComp-E4G / (4S)-4-[(1R)-1-hydroxy-2-({[3-(propan-2-yl)phenyl]methyl}amino)ethyl]-19-(2-oxopropoxy)-11,16-dioxa-3-azatricyclo[15.3.1.1~6,10~]docosa-1(21),6(22),7,9,17,19-hexaen-2-one Mass: 574.707 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₃₄H₄₂N₂O₆
#3: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 235 / Source method: isolated from a natural source / Formula: H₂O
Has protein modification	Y

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 3.01 Å³/Da / Density % sol: 59.11 %
Crystal grow	Temperature: 292 K / Method: hanging drop / pH: 5 Details: CRYSTALS WERE GROWN AT 19C BY VAPOUR DIFFUSION IN HANGING DROPS FROM 1.0M AMMONIUM PHOSPHATE, 0.1M SODIUM CITRATE PH 5.0. PROTEIN STOCK WAS BACE MUT46B BATCH XIII 8.3MG/ML IN 10MM TRIS-HCL ...Details: CRYSTALS WERE GROWN AT 19C BY VAPOUR DIFFUSION IN HANGING DROPS FROM 1.0M AMMONIUM PHOSPHATE, 0.1M SODIUM CITRATE PH 5.0. PROTEIN STOCK WAS BACE MUT46B BATCH XIII 8.3MG/ML IN 10MM TRIS-HCL PH 7.4, 25MM NACL, WITH A 5-FOLD EXCESS OF BMC018 ADDED FROM A 50MM STOCK SOLUTION IN DMSO (2.0% DMSO IN DROP). CRYO-PROTECTANT WAS 1.2M AMMONIUM PHOSPHATE, 0.1M SODIUM CITRATE PH 5.0, 25%(V/V) GLYCEROL, 2.0% DMSO, 1MM BMC018.

Crystal

Density Matthews: 3.01 Å³/Da / Density % sol: 59.11 %

Crystal grow

Temperature: 292 K / Method: hanging drop / pH: 5
Details: CRYSTALS WERE GROWN AT 19C BY VAPOUR DIFFUSION IN HANGING DROPS FROM 1.0M AMMONIUM PHOSPHATE, 0.1M SODIUM CITRATE PH 5.0. PROTEIN STOCK WAS BACE MUT46B BATCH XIII 8.3MG/ML IN 10MM TRIS-HCL ...

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Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: ROTATING ANODE / Type: RIGAKU FR-E / Wavelength: 1.54178
Detector	Type: MAR scanner 345 mm plate / Detector: IMAGE PLATE / Date: Sep 19, 2005
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.54178 Å / Relative weight: 1
Reflection	Resolution: 2.45→97.271 Å / Num. obs: 59766 / % possible obs: 99.4 % / R_merge(I) obs: 0.062

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Phasing

Phasing	Method: molecular replacement

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Processing

Software

Name	Version	Classification
PHENIX	1.12_2829	refinement
CNX		refinement
CNX		phasing
SCALEPACK		data scaling
HKL-2000		date reduction
PDB_EXTRACT	3.24	data extraction

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.45→19.39 Å / SU ML: 0.24 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 20.12 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.195	3011	5.05 %
R_work	0.164	-	-
obs	0.166	59594	99.9 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL

Refinement step

Cycle: LAST / Resolution: 2.45→19.39 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	8903	0	126	235	9264

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.008	9275
X-RAY DIFFRACTION	f_angle_d	1.067	12610
X-RAY DIFFRACTION	f_dihedral_angle_d	6.474	5385
X-RAY DIFFRACTION	f_chiral_restr	0.063	1360
X-RAY DIFFRACTION	f_plane_restr	0.006	1618

LS refinement shell

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Refine-ID	% reflection obs (%)
2.45-2.4882	0.2796	125	0.2103	2577	X-RAY DIFFRACTION	100
2.4882-2.5289	0.2545	159	0.1874	2550	X-RAY DIFFRACTION	100
2.5289-2.5724	0.2466	130	0.1852	2551	X-RAY DIFFRACTION	100
2.5724-2.6191	0.2572	134	0.1866	2554	X-RAY DIFFRACTION	100
2.6191-2.6693	0.2298	140	0.1867	2545	X-RAY DIFFRACTION	100
2.6693-2.7237	0.2404	149	0.1977	2561	X-RAY DIFFRACTION	100
2.7237-2.7827	0.2644	116	0.1953	2586	X-RAY DIFFRACTION	100
2.7827-2.8472	0.2408	135	0.1861	2562	X-RAY DIFFRACTION	100
2.8472-2.9182	0.2287	143	0.1841	2553	X-RAY DIFFRACTION	100
2.9182-2.9968	0.2362	150	0.184	2572	X-RAY DIFFRACTION	100
2.9968-3.0847	0.2237	114	0.1854	2560	X-RAY DIFFRACTION	100
3.0847-3.1838	0.2304	130	0.1917	2582	X-RAY DIFFRACTION	100
3.1838-3.2971	0.2297	139	0.1916	2573	X-RAY DIFFRACTION	100
3.2971-3.4284	0.2195	127	0.1772	2593	X-RAY DIFFRACTION	100
3.4284-3.5835	0.2249	131	0.1657	2576	X-RAY DIFFRACTION	100
3.5835-3.7711	0.1955	135	0.1594	2585	X-RAY DIFFRACTION	100
3.7711-4.0055	0.1663	143	0.1441	2556	X-RAY DIFFRACTION	100
4.0055-4.3116	0.1623	140	0.1399	2583	X-RAY DIFFRACTION	100
4.3116-4.7397	0.1393	145	0.1232	2578	X-RAY DIFFRACTION	100
4.7397-5.4125	0.1773	155	0.1394	2566	X-RAY DIFFRACTION	100
5.4125-6.7706	0.1931	120	0.1666	2618	X-RAY DIFFRACTION	100
6.7706-19.3858	0.1521	151	0.1652	2602	X-RAY DIFFRACTION	99

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	0.0268	0.0304	-0.0866	0.2184	-0.0431	0.2902	-0.2929	-0.3319	0.3267	0.5172	0.1016	-0.3095	-0.1093	-0.0214	-0.0441	0.4314	-0.0082	-0.089	0.3874	0.0001	0.344	44.3147	9.4751	26.5853
2	0.4795	-0.1832	0.2358	0.99	-0.3377	0.8221	0.0018	0.193	0.2559	-0.0284	-0.0906	-0.0344	-0.2663	0.1284	0.0001	0.4807	-0.0406	-0.0502	0.4022	0.0699	0.3613	41.7258	15.5736	13.4934
3	0.488	-0.132	0.3998	0.89	0.1085	0.4061	-0.0913	0.1145	0.1416	0.1231	-0.0268	-0.2292	-0.1496	0.0552	-0.0008	0.3821	-0.0102	-0.0138	0.3826	0.002	0.2577	45.3806	1.0166	17.7884
4	0.8558	0.09	-0.3367	1.3802	-0.4649	1.0533	0.0091	0.2221	-0.0496	0.0363	0.1601	0.3047	-0.1394	-0.1054	0.0368	0.2915	0.0557	0.0057	0.2808	0.0263	0.3023	23.0486	-7.9746	20.7056
5	0.1366	-0.1532	0.1557	0.6621	-0.5971	0.5356	0.0458	0.1305	-0.0217	0.2156	0.122	0.069	-0.1436	-0.1295	0.0011	0.367	0.0594	0.0861	0.3074	-0.0065	0.3285	25.3525	-9.8056	29.5317
6	2.0207	-0.0272	0.8939	0.0099	-0.0172	0.4067	-0.0965	0.2454	0.5026	0.1001	0.0709	0.3215	-0.4949	-0.0754	0.0594	0.5043	0.1362	0.062	0.1685	0.0384	0.4084	22.074	3.3267	27.4918
7	0.4291	-0.4603	0.3009	0.7695	-0.4623	0.4597	-0.0267	0.066	-0.1297	0.0372	0.061	0.1801	-0.1446	-0.1617	-0.0002	0.3721	0.0636	0.0583	0.3405	-0.0115	0.2687	34.3855	-13.0542	24.6496
8	2.0038	0.5324	0.2219	0.8501	0.2289	1.7635	0.0658	-0.1757	-0.2855	0.0484	-0.0662	0.0303	-0.0352	-0.3282	-0.0004	0.2541	0.0088	-0.0239	0.3154	0.0683	0.2967	16.7453	13.911	-12.5708
9	1.1038	-0.1799	0.367	0.3391	-0.0664	1.529	0.0699	0.2706	-0.9043	-0.0615	0.0421	-0.463	0.332	0.0886	0.1256	0.3507	0.0248	-0.0283	0.1988	-0.1046	0.8241	34.4896	-1.6785	-22.5937
10	1.5983	0.9229	0.1767	0.5486	0.0444	0.7604	0.0442	0.0935	-0.4639	0.0289	-0.0237	-0.1632	0.0445	0.0295	0.0037	0.3244	0.0089	-0.0229	0.2556	0.0302	0.4143	33.2555	11.5466	-19.7921
11	0.4125	-0.2738	0.086	0.2061	-0.1272	0.1931	-0.1437	0.1667	0.1555	-0.0026	0.0394	0.0625	-0.0027	-0.7181	-0.0008	0.3607	-0.01	-0.0308	0.4475	-0.0105	0.4162	-1.4581	-48.2758	35.6041
12	0.7144	-0.0939	-0.7336	0.6879	-0.1872	1.102	-0.0928	-0.1217	-0.0874	0.1257	-0.0804	0.1393	0.2406	-0.2583	-0.0002	0.4044	-0.057	-0.0086	0.3777	0.056	0.4074	1.9503	-54.7286	48.4066
13	0.7002	0.584	-0.7651	0.8682	-0.2379	1.1825	-0.1032	0.0364	-0.2046	-0.0237	-0.0155	-0.1528	0.1339	-0.01	-0.0009	0.3148	0.0598	-0.0344	0.3052	0.03	0.3822	13.3507	-48.3844	35.097
14	0.2891	-0.261	-0.1698	0.5301	0.0122	0.348	0.1548	-0.2692	0.0235	0.2215	0.0607	-0.0732	-0.1245	0.1041	0.001	0.3285	-0.0373	0.0335	0.3485	-0.0142	0.3291	21.6496	-27.7904	43.4675
15	0.3828	0.2529	0.2342	0.7794	-0.5877	1.3295	0.1441	-0.0684	0.1233	0.2461	0.1488	0.0812	-0.3049	-0.2888	0.0187	0.4146	0.112	0.119	0.395	0.0608	0.3971	8.8949	-23.1658	41.381
16	0.4389	0.133	-0.299	0.6389	0.1451	0.7272	0.0248	-0.0505	-0.1389	-0.0193	-0.0771	-0.0434	-0.1114	-0.027	0.0006	0.3075	0.0683	-0.011	0.3387	0.0382	0.3473	17.6517	-34.9625	32.8015

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	CHAIN 'A' AND (RESID 46P THROUGH 24 )
2	X-RAY DIFFRACTION	2	CHAIN 'A' AND (RESID 25 THROUGH 116 )
3	X-RAY DIFFRACTION	3	CHAIN 'A' AND (RESID 117 THROUGH 183 )
4	X-RAY DIFFRACTION	4	CHAIN 'A' AND (RESID 184 THROUGH 270 )
5	X-RAY DIFFRACTION	5	CHAIN 'A' AND (RESID 271 THROUGH 308 )
6	X-RAY DIFFRACTION	6	CHAIN 'A' AND (RESID 309 THROUGH 340 )
7	X-RAY DIFFRACTION	7	CHAIN 'A' AND (RESID 341 THROUGH 385 )
8	X-RAY DIFFRACTION	8	CHAIN 'B' AND (RESID 46P THROUGH 233 )
9	X-RAY DIFFRACTION	9	CHAIN 'B' AND (RESID 234 THROUGH 317 )
10	X-RAY DIFFRACTION	10	CHAIN 'B' AND (RESID 318 THROUGH 385 )
11	X-RAY DIFFRACTION	11	CHAIN 'C' AND (RESID 46P THROUGH 24 )
12	X-RAY DIFFRACTION	12	CHAIN 'C' AND (RESID 25 THROUGH 116 )
13	X-RAY DIFFRACTION	13	CHAIN 'C' AND (RESID 117 THROUGH 202 )
14	X-RAY DIFFRACTION	14	CHAIN 'C' AND (RESID 203 THROUGH 252 )
15	X-RAY DIFFRACTION	15	CHAIN 'C' AND (RESID 253 THROUGH 327 )
16	X-RAY DIFFRACTION	16	CHAIN 'C' AND (RESID 328 THROUGH 385 )

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