PDB-5qda: Crystal structure of BACE complex with BMC013

ID or keywords:

Entry

Database: PDB / ID: 5qda

Title

Crystal structure of BACE complex with BMC013

Components

Beta-secretase 1

Keywords

HYDROLASE / Hydroloase / D3R / BACE / Ligand Docking

Function / homology

Function and homology information

memapsin 2 / Golgi-associated vesicle lumen / signaling receptor ligand precursor processing / beta-aspartyl-peptidase activity / amyloid precursor protein catabolic process / amyloid-beta formation / membrane protein ectodomain proteolysis / amyloid-beta metabolic process / cellular response to manganese ion / prepulse inhibition ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT /

molecular replacement / Resolution: 2.1 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	Oct 23, 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	5qda.cif.gz	463.6 KB	Display	PDBx/mmCIF format
PDB format	pdb5qda.ent.gz	383.1 KB	Display	PDB format
PDBx/mmJSON format	5qda.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	5qda_validation.pdf.gz	1.3 MB	Display	wwPDB validaton report
Full document	5qda_full_validation.pdf.gz	1.3 MB	Display
Data in XML	5qda_validation.xml.gz	42.7 KB	Display
Data in CIF	5qda_validation.cif.gz	60.8 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/qd/5qda ftp://data.pdbj.org/pub/pdb/validation_reports/qd/5qda	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	4lxa-1 5qcp-2 5qd6-1 4acx-d 5qd6-2 5qcz-1 5ygy-d 2q11-3 5qd9-1 7b1e-d 6bfd-1 3k5f-1 6dhc-3 3qbh-2 3msk-d 5qcx-2 3dv1-1 2f3f-1 2qzk-d 2p4j-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
45.3 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Beta-secretase 1

hetero molecules

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

3

C: Beta-secretase 1

hetero molecules

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

Unit cell

Length a, b, c (Å)	82.597, 104.059, 100.050
Angle α, β, γ (deg.)	90.00, 104.66, 90.00
Int Tables number	4
Space group name H-M	P12₁1

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID
1	1
2	1
3	1

NCS domain segments:

Dom-ID	Component-ID	Ens-ID	Selection details
1	1	1	CHAIN A
2	1	1	CHAIN B
3	1	1	(CHAIN C AND (RESID -2 THROUGH 157 OR RESID 169 THROUGH 385))

#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-E74 / (4S)-4-[(1R)-1-hydroxy-2-({[3-(propan-2-yl)phenyl]methyl}amino)ethyl]-18-methoxy-3,15,17-triazatricyclo[14.3.1.1~6,10~]henicosa-1(20),6(21),7,9,16,18-hexaen-2-one Mass: 516.674 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₃₁H₄₀N₄O₃
#3: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 345 / 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: 3.1 Å³/Da / Density % sol: 60.28 %
Crystal grow	Temperature: 292 K / Method: hanging drop Details: CRYSTALS WERE GROWN AT 19C BY VAPOUR DIFFUSION IN HANGING DROPS FROM 1.0M AMMONIUM SULFATE. PROTEIN STOCK WAS BACE MUT46B BATCH XII 8.45MG/ML IN 10MM TRIS-HCL PH 7.4, 25MM NACL, WITH A 4- ...Details: CRYSTALS WERE GROWN AT 19C BY VAPOUR DIFFUSION IN HANGING DROPS FROM 1.0M AMMONIUM SULFATE. PROTEIN STOCK WAS BACE MUT46B BATCH XII 8.45MG/ML IN 10MM TRIS-HCL PH 7.4, 25MM NACL, WITH A 4-FOLD EXCESS OF BMC013 ADDED FROM A 50MM STOCK SOLUTION IN DMSO (1.4% DMSO IN DROP). CRYO-PROTECTANT WAS 20%(V/V) GLYCEROL, 80% (V/V) RESERVOIR SOLUTION

Crystal

Density Matthews: 3.1 Å³/Da / Density % sol: 60.28 %

Crystal grow

Temperature: 292 K / Method: hanging drop
Details: CRYSTALS WERE GROWN AT 19C BY VAPOUR DIFFUSION IN HANGING DROPS FROM 1.0M AMMONIUM SULFATE. PROTEIN STOCK WAS BACE MUT46B BATCH XII 8.45MG/ML IN 10MM TRIS-HCL PH 7.4, 25MM NACL, WITH A 4- ...

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Data collection

Diffraction	Mean temperature: 105 K
Diffraction source	Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.97936
Detector	Type: MAR CCD 165 mm / Detector: CCD / Date: Sep 2, 2004
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97936 Å / Relative weight: 1
Reflection	Resolution: 2.1→41.985 Å / Num. obs: 93508 / % possible obs: 98 % / R_merge(I) obs: 0.063

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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
DENZO		date reduction
PDB_EXTRACT	3.24	data extraction

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.1→41.99 Å / SU ML: 0.24 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 22.4 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.209	4692	5.02 %
R_work	0.181	-	-
obs	0.182	93508	98 %

Solvent computation

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

Displacement parameters

B_iso mean: 53.85 Å²

Refinement step

Cycle: LAST / Resolution: 2.1→41.99 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	8925	0	114	345	9384

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.008	9287
X-RAY DIFFRACTION	f_angle_d	0.899	12628
X-RAY DIFFRACTION	f_dihedral_angle_d	15.115	5424
X-RAY DIFFRACTION	f_chiral_restr	0.06	1362
X-RAY DIFFRACTION	f_plane_restr	0.006	1620

Refine LS restraints NCS

Ens-ID	Dom-ID	Auth asym-ID	Number	Refine-ID	Type
1	1	A	5446	X-RAY DIFFRACTION	POSITIONAL
1	2	B	5446	X-RAY DIFFRACTION	POSITIONAL
1	3	C	5446	X-RAY DIFFRACTION	POSITIONAL

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 (%)
2.1001-2.1239	0.2904	152	0.2251	2826	X-RAY DIFFRACTION	93
2.1239-2.1489	0.258	146	0.2208	2860	X-RAY DIFFRACTION	96
2.1489-2.1751	0.2507	152	0.2102	2956	X-RAY DIFFRACTION	97
2.1751-2.2027	0.2666	159	0.2182	2864	X-RAY DIFFRACTION	97
2.2027-2.2316	0.3477	169	0.3079	2954	X-RAY DIFFRACTION	97
2.2316-2.2622	0.3828	143	0.3641	2923	X-RAY DIFFRACTION	97
2.2622-2.2945	0.3454	180	0.2791	2936	X-RAY DIFFRACTION	97
2.2945-2.3288	0.2653	153	0.2078	2917	X-RAY DIFFRACTION	98
2.3288-2.3651	0.2631	149	0.1958	2966	X-RAY DIFFRACTION	98
2.3651-2.4039	0.2281	151	0.1971	2939	X-RAY DIFFRACTION	98
2.4039-2.4454	0.2461	150	0.1926	2970	X-RAY DIFFRACTION	98
2.4454-2.4898	0.2372	131	0.1951	2976	X-RAY DIFFRACTION	98
2.4898-2.5377	0.2319	149	0.1868	2941	X-RAY DIFFRACTION	98
2.5377-2.5895	0.2283	155	0.1853	2968	X-RAY DIFFRACTION	98
2.5895-2.6458	0.228	140	0.1955	2987	X-RAY DIFFRACTION	98
2.6458-2.7073	0.2457	162	0.211	2947	X-RAY DIFFRACTION	98
2.7073-2.775	0.2735	174	0.2084	2957	X-RAY DIFFRACTION	98
2.775-2.85	0.246	158	0.1964	2973	X-RAY DIFFRACTION	98
2.85-2.9339	0.222	166	0.1925	2956	X-RAY DIFFRACTION	99
2.9339-3.0286	0.2047	158	0.1963	2975	X-RAY DIFFRACTION	98
3.0286-3.1368	0.2493	144	0.194	3001	X-RAY DIFFRACTION	99
3.1368-3.2623	0.2232	150	0.2051	2991	X-RAY DIFFRACTION	99
3.2623-3.4107	0.2195	143	0.1964	3003	X-RAY DIFFRACTION	99
3.4107-3.5905	0.2151	167	0.1781	2996	X-RAY DIFFRACTION	99
3.5905-3.8153	0.1817	149	0.1737	2980	X-RAY DIFFRACTION	99
3.8153-4.1096	0.1797	170	0.1512	2977	X-RAY DIFFRACTION	99
4.1096-4.5228	0.1637	173	0.1342	3004	X-RAY DIFFRACTION	99
4.5228-5.1762	0.1609	174	0.1314	3015	X-RAY DIFFRACTION	99
5.1762-6.5175	0.1856	170	0.17	3015	X-RAY DIFFRACTION	99
6.5175-41.993	0.1788	155	0.1774	3043	X-RAY DIFFRACTION	97

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	0.9296	-0.0543	0.0651	1.6057	-0.4006	0.8965	-0.0822	0.1425	0.0899	0.0059	-0.0024	-0.1065	-0.1491	0.154	-0.0001	0.3891	-0.0323	-0.0179	0.3757	0.0192	0.2626	40.2147	4.898	16.9958
2	1.2431	0.2452	-0.1806	1.1798	-0.8119	1.0763	0.0119	0.1521	0.1131	0.2203	0.17	0.3666	-0.2343	-0.0951	0.0146	0.3751	0.0759	0.0781	0.2975	0.0377	0.4198	20.224	-3.6447	27.3137
3	0.4206	-0.3632	0.1507	1.214	-0.8472	0.5299	-0.0435	0.0187	-0.1139	-0.0009	0.0421	0.1752	-0.045	-0.087	0.0006	0.3714	0.0351	0.0573	0.3659	-0.04	0.3099	34.394	-13.1512	24.559
4	2.1789	0.506	0.5259	0.8408	0.2071	1.594	0.0956	-0.291	-0.2559	0.0486	-0.0841	0.0072	0.01	-0.3446	0.0002	0.316	-0.0126	-0.003	0.3761	0.052	0.3174	17.1853	14.1389	-12.5212
5	1.8697	-0.3799	0.4268	0.6621	-0.4451	1.5022	0.1619	0.2131	-0.8576	-0.1562	-0.0786	-0.2759	0.4025	0.1102	0.0488	0.4556	0.0205	-0.0071	0.2266	-0.0728	0.6944	33.4852	-0.7521	-22.1681
6	1.4065	0.8755	0.1492	0.6458	0.218	0.255	0.0675	0.0782	-0.2508	0.111	-0.0359	-0.1913	-0.2059	0.2563	0.0002	0.3381	0.0145	-0.0143	0.3351	0.0516	0.3868	36.1899	16.0565	-19.2536
7	0.0889	-0.0508	-0.283	0.1117	-0.2254	0.6372	0.1151	-0.0831	-0.2284	-0.1287	-0.0658	-0.0091	0.2539	-0.3435	-0.0002	0.3848	-0.0162	-0.068	0.4436	0.0221	0.4532	0.2818	-49.4791	38.3159
8	0.9033	0.4676	-0.1488	1.038	-0.363	1.7301	0.097	-0.0435	-0.1829	-0.047	0.0063	0.0851	0.3279	-0.1954	-0	0.381	-0.0139	-0.0543	0.357	0.0511	0.4516	4.4245	-53.7543	44.0757
9	1.1406	0.014	-0.3831	0.969	-0.1901	0.5346	0.1024	-0.1518	0.0032	0.022	-0.0513	-0.0653	-0.0739	0.1047	-0.0001	0.3457	0.017	-0.0045	0.3802	0.0153	0.3963	20.2463	-33.592	38.6807
10	0.321	0.0279	0.1086	0.592	-0.8594	1.2439	0.0926	0.0201	0.096	0.0425	0.1779	0.0127	-0.2723	-0.144	0.0005	0.3224	0.0734	0.0666	0.356	0.023	0.3875	11.2369	-23.1425	39.3544
11	0.6232	0.1846	0.1838	0.4475	0.0371	0.3591	0.329	-0.152	-0.1657	0.3209	0.0809	0.3982	0.1443	-0.3097	0.173	0.3796	0.0426	0.1541	0.5084	0.0822	0.4653	5.2927	-28.233	44.4173
12	0.4535	0.3576	-0.1205	0.4363	0.0485	0.861	-0.0161	0.0874	-0.0868	-0.1701	-0.0011	-0.118	-0.071	0.0858	0.0001	0.338	0.0841	-0.01	0.3605	0.0152	0.3985	18.5254	-35.0255	30.4759

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	CHAIN 'A' AND (RESID -2 THROUGH 233 )
2	X-RAY DIFFRACTION	2	CHAIN 'A' AND (RESID 234 THROUGH 340 )
3	X-RAY DIFFRACTION	3	CHAIN 'A' AND (RESID 341 THROUGH 385 )
4	X-RAY DIFFRACTION	4	CHAIN 'B' AND (RESID -2 THROUGH 233 )
5	X-RAY DIFFRACTION	5	CHAIN 'B' AND (RESID 234 THROUGH 340 )
6	X-RAY DIFFRACTION	6	CHAIN 'B' AND (RESID 341 THROUGH 385 )
7	X-RAY DIFFRACTION	7	CHAIN 'C' AND (RESID -2 THROUGH 41 )
8	X-RAY DIFFRACTION	8	CHAIN 'C' AND (RESID 42 THROUGH 176 )
9	X-RAY DIFFRACTION	9	CHAIN 'C' AND (RESID 177 THROUGH 251 )
10	X-RAY DIFFRACTION	10	CHAIN 'C' AND (RESID 252 THROUGH 309 )
11	X-RAY DIFFRACTION	11	CHAIN 'C' AND (RESID 310 THROUGH 340 )
12	X-RAY DIFFRACTION	12	CHAIN 'C' AND (RESID 341 THROUGH 385 )

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