PDB-5qd3: Crystal structure of BACE complex with BMC010

ID or keywords:

Entry

Database: PDB / ID: 5qd3

Title

Crystal structure of BACE complex with BMC010

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 / detection of mechanical stimulus involved in sensory perception of pain / amyloid-beta metabolic process / cellular response to manganese ion ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

MOLECULAR REPLACEMENT /

molecular replacement / Resolution: 2.46 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	5qd3.cif.gz	461.3 KB	Display	PDBx/mmCIF format
PDB format	pdb5qd3.ent.gz	381.1 KB	Display	PDB format
PDBx/mmJSON format	5qd3.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	5qd3_validation.pdf.gz	1.4 MB	Display	wwPDB validaton report
Full document	5qd3_full_validation.pdf.gz	1.4 MB	Display
Data in XML	5qd3_validation.xml.gz	42.4 KB	Display
Data in CIF	5qd3_validation.cif.gz	60.9 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/qd/5qd3 ftp://data.pdbj.org/pub/pdb/validation_reports/qd/5qd3	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	3ckp-2 5qd2-3 3rtm-d 1ym2-3 1ym2-2 5qcv-2 3ixk-1 5qco-3 2ph8-d 5qcu-3 4ke0-2 3kxy-4 5qcw-2 4d8c-1 4d85-d 1w51-d 5qco-1 1ym4-1 5qd2-1 2i0e-1 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)	82.972, 104.667, 100.887
Angle α, β, γ (deg.)	90.00, 104.31, 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-E6M / (10R,12S)-12-[(1R)-1-hydroxy-2-({[3-(propan-2-yl)phenyl]methyl}amino)ethyl]-17-(methoxymethyl)-10-methyl-2,13-diazabicyclo[13.3.1]nonadeca-1(19),15,17-trien-14-one Mass: 523.750 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₃₂H₄₉N₃O₃
#3: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 353 / 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: 3.16 Å³/Da / Density % sol: 61.08 %
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 IN WATER. PROTEIN STOCK WAS BACE MUT46B BATCH XVI 7.0MG/ML IN 10MM TRIS-HCL PH 7.4, 25MM NACL, WITH ...Details: CRYSTALS WERE GROWN AT 19C BY VAPOUR DIFFUSION IN HANGING DROPS FROM 1.0M AMMONIUM SULFATE IN WATER. PROTEIN STOCK WAS BACE MUT46B BATCH XVI 7.0MG/ML IN 10MM TRIS-HCL PH 7.4, 25MM NACL, WITH A 6-FOLD EXCESS OF BMC010 ADDED FROM A 50MM STOCK SOLUTION IN 90% DMSO-D6 (1.7% DMSO IN DROP). A SOLUTION CONTAINING 1.2M AMMONIUM SULFATE, 25% GLYCEROL, 1MM BMC010 AND 1.8% DMSO WAS USED AS CRYO-PROTECTANT.

Crystal

Density Matthews: 3.16 Å³/Da / Density % sol: 61.08 %

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 IN WATER. PROTEIN STOCK WAS BACE MUT46B BATCH XVI 7.0MG/ML IN 10MM TRIS-HCL PH 7.4, 25MM NACL, WITH ...

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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 21, 2006
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.54178 Å / Relative weight: 1
Reflection	Resolution: 2.46→71.346 Å / Num. obs: 60702 / % possible obs: 99.9 % / 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
HKL-2000		date reduction
PDB_EXTRACT	3.24	data extraction

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.46→71.35 Å / SU ML: 0.24 / Cross valid method: THROUGHOUT / σ(F): 1.38 / Phase error: 19.39 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.2	6084	10.02 %
R_work	0.164	-	-
obs	0.168	60702	99.9 %

Solvent computation

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

Displacement parameters

B_iso mean: 47.78 Å²

Refinement step

Cycle: LAST / Resolution: 2.46→71.35 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	8907	0	114	353	9374

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.008	9264
X-RAY DIFFRACTION	f_angle_d	0.905	12591
X-RAY DIFFRACTION	f_dihedral_angle_d	14.713	5419
X-RAY DIFFRACTION	f_chiral_restr	0.058	1363
X-RAY DIFFRACTION	f_plane_restr	0.006	1613

Refine LS restraints NCS

Ens-ID	Dom-ID	Auth asym-ID	Number	Refine-ID	Type
1	1	A	5428	X-RAY DIFFRACTION	POSITIONAL
1	2	B	5428	X-RAY DIFFRACTION	POSITIONAL
1	3	C	5428	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 (%)
2.4601-2.488	0.2855	215	0.2096	1777	X-RAY DIFFRACTION	100
2.488-2.5173	0.2717	204	0.1975	1838	X-RAY DIFFRACTION	100
2.5173-2.548	0.2361	187	0.1894	1805	X-RAY DIFFRACTION	100
2.548-2.5802	0.2291	212	0.1833	1818	X-RAY DIFFRACTION	100
2.5802-2.6142	0.2303	204	0.1711	1809	X-RAY DIFFRACTION	100
2.6142-2.65	0.2487	215	0.1828	1789	X-RAY DIFFRACTION	100
2.65-2.6879	0.2332	201	0.1814	1821	X-RAY DIFFRACTION	100
2.6879-2.728	0.2166	206	0.1854	1798	X-RAY DIFFRACTION	100
2.728-2.7706	0.2428	209	0.1869	1822	X-RAY DIFFRACTION	100
2.7706-2.816	0.2271	203	0.1829	1797	X-RAY DIFFRACTION	100
2.816-2.8646	0.2264	212	0.1768	1810	X-RAY DIFFRACTION	100
2.8646-2.9167	0.2326	172	0.1793	1860	X-RAY DIFFRACTION	100
2.9167-2.9728	0.2345	214	0.1793	1828	X-RAY DIFFRACTION	100
2.9728-3.0335	0.2233	193	0.1785	1800	X-RAY DIFFRACTION	100
3.0335-3.0994	0.2319	196	0.18	1824	X-RAY DIFFRACTION	100
3.0994-3.1715	0.2403	197	0.1881	1834	X-RAY DIFFRACTION	100
3.1715-3.2508	0.2408	190	0.1838	1823	X-RAY DIFFRACTION	100
3.2508-3.3387	0.2085	185	0.1801	1826	X-RAY DIFFRACTION	100
3.3387-3.437	0.2098	214	0.1789	1806	X-RAY DIFFRACTION	100
3.437-3.5479	0.2071	202	0.1656	1815	X-RAY DIFFRACTION	100
3.5479-3.6747	0.2055	201	0.1716	1820	X-RAY DIFFRACTION	100
3.6747-3.8218	0.1892	195	0.1568	1846	X-RAY DIFFRACTION	100
3.8218-3.9958	0.1766	194	0.1401	1816	X-RAY DIFFRACTION	100
3.9958-4.2064	0.1689	209	0.1443	1828	X-RAY DIFFRACTION	100
4.2064-4.4699	0.159	213	0.131	1818	X-RAY DIFFRACTION	100
4.4699-4.815	0.1418	205	0.1199	1836	X-RAY DIFFRACTION	100
4.815-5.2994	0.1683	216	0.143	1821	X-RAY DIFFRACTION	100
5.2994-6.0659	0.2125	219	0.1595	1828	X-RAY DIFFRACTION	100
6.0659-7.6409	0.1962	203	0.1729	1849	X-RAY DIFFRACTION	100
7.6409-71.3761	0.1732	198	0.1793	1856	X-RAY DIFFRACTION	98

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	0.7771	-0.1576	0.3048	1.2783	-0.275	0.7355	-0.044	0.1674	0.0961	0.0286	-0.0241	-0.0439	-0.1705	0.113	-0.0002	0.26	-0.0236	-0.0221	0.2221	0.021	0.1206	40.5223	4.9857	17.0207
2	0.7071	-0.0079	0.1289	0.4183	-0.4535	0.6585	-0.0367	0.0468	-0.0337	0.1976	0.1958	0.4057	-0.1782	-0.0867	0.2564	0.289	0.0908	0.1172	0.1948	0.0415	0.3395	19.0621	-4.1944	28.4314
3	0.4822	-0.0251	-0.1492	0.7107	-0.3518	0.2863	-0.0025	0.1154	-0.0707	0.087	0.0552	0.1934	-0.1732	0.0524	0.0036	0.2753	0.0512	0.0406	0.2063	0.0107	0.1893	31.2005	-9.1696	24.369
4	1.6166	0.4063	0.1842	0.686	0.1483	1.2003	0.0748	-0.1525	-0.221	0.0534	-0.0561	0.0238	0.0077	-0.2533	-0	0.2003	-0.0158	-0.0109	0.2513	0.0417	0.2063	17.2706	14.3123	-12.7591
5	0.6166	-0.264	0.233	0.299	0.0129	0.8597	0.123	0.2226	-0.6917	-0.0892	-0.0689	-0.3821	0.2664	0.026	0.0607	0.3222	-0.0096	-0.0482	0.1232	-0.0861	0.602	33.8534	-0.6641	-22.7647
6	0.7057	0.5102	-0.0785	0.3737	0.0385	0.3149	-0.0449	0.1568	-0.2656	0.1355	0.0347	-0.1574	-0.0867	0.0888	-0.0018	0.209	0.0163	-0.01	0.2429	0.0285	0.3106	36.489	16.2846	-19.5209
7	0.7067	0.3088	-0.5482	0.8995	-0.2888	1.0684	0.0489	-0.0433	-0.083	0.0159	-0.0298	-0.0347	0.111	-0.0909	-0.0001	0.1882	0.0076	-0.0276	0.2212	0.0319	0.2597	8.8943	-46.8993	42.03
8	0.2312	0.122	0.3348	0.7702	-0.1844	0.6451	0.0881	-0.0083	0.1424	0.1973	0.2068	0.0586	-0.0362	-0.2504	0.1782	0.2499	0.0839	0.14	0.325	0.0887	0.3383	8.6903	-23.1093	41.6234
9	0.3695	0.4332	-0.1234	0.4296	-0.0851	0.4574	0.0867	-0.0042	-0.1001	0.0249	-0.0461	-0.0766	-0.0023	0.0558	-0	0.2115	0.0558	-0.0004	0.2518	0.0302	0.2782	17.5142	-35.0663	32.9562

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 317 )
3	X-RAY DIFFRACTION	3	CHAIN 'A' AND (RESID 318 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 252 )
8	X-RAY DIFFRACTION	8	CHAIN 'C' AND (RESID 253 THROUGH 327 )
9	X-RAY DIFFRACTION	9	CHAIN 'C' AND (RESID 328 THROUGH 385 )

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