PDB-5qd8: Crystal structure of BACE complex with BMC003

ID or keywords:

Entry

Database: PDB / ID: 5qd8

Title

Crystal structure of BACE complex with BMC003

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 / cellular response to manganese ion / amyloid-beta metabolic process / prepulse inhibition ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT /

molecular replacement / Resolution: 2.45 Å

Model details

Structures for D3R docking challenge

Authors

Ostermann, N. / 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

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	5qd8.cif.gz	451.7 KB	Display	PDBx/mmCIF format
PDB format	pdb5qd8.ent.gz	385.9 KB	Display	PDB format
PDBx/mmJSON format	5qd8.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	5qd8_validation.pdf.gz	1.4 MB	Display	wwPDB validaton report
Full document	5qd8_full_validation.pdf.gz	1.4 MB	Display
Data in XML	5qd8_validation.xml.gz	40.3 KB	Display
Data in CIF	5qd8_validation.cif.gz	55.9 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/qd/5qd8 ftp://data.pdbj.org/pub/pdb/validation_reports/qd/5qd8	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 5qd3-3 4lxa-2 2wf4-d 2wf2-d 2vj6-d 5qd2-2 5qcw-3 4d83-1 3s2o-d 2f3e-3 1ym2-2 5qcu-3 2vkm-4 5qd7-1 3pi5-2 4ke0-2 3k5d-1 5qd2-1 4lxm-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)	82.678, 105.557, 99.941
Angle α, β, γ (deg.)	90.00, 103.97, 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-E6V / (3S,14R,16S)-16-[(1R)-2-{[(4S)-2,2-dimethyl-6-(propan-2-yl)-3,4-dihydro-2H-1-benzopyran-4-yl]amino}-1-hydroxyethyl]-3,4,14-trimethyl-1,4-diazacyclohexadecane-2,5-dione Mass: 557.807 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₃₃H₅₅N₃O₄
#3: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 87 / 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: 3.15 Å³/Da / Density % sol: 60.96 %
Crystal grow	Temperature: 292 K / Method: hanging drop Details: HANGING DROP, VAPOR DIFFUSION, 1 UL PROTEIN + 1 UL RESERVOIR; PROTEIN SOLUTION: 9.3 MG/ML BACE MUT46B, 10 MM TRIS PH 7.4, 25 MM NACL, 1MM BMC003; RESERVOIR SOLUTION: 1.1M AMMONIUM SULFATE; ...Details: HANGING DROP, VAPOR DIFFUSION, 1 UL PROTEIN + 1 UL RESERVOIR; PROTEIN SOLUTION: 9.3 MG/ML BACE MUT46B, 10 MM TRIS PH 7.4, 25 MM NACL, 1MM BMC003; RESERVOIR SOLUTION: 1.1M AMMONIUM SULFATE; CRYO: DROP PLUS 2 UL RESERVOIR SOLUTION PLUS 0.5 UL GLYCEROL.

Crystal

Density Matthews: 3.15 Å³/Da / Density % sol: 60.96 %

Crystal grow

Temperature: 292 K / Method: hanging drop
Details: HANGING DROP, VAPOR DIFFUSION, 1 UL PROTEIN + 1 UL RESERVOIR; PROTEIN SOLUTION: 9.3 MG/ML BACE MUT46B, 10 MM TRIS PH 7.4, 25 MM NACL, 1MM BMC003; RESERVOIR SOLUTION: 1.1M AMMONIUM SULFATE; ...

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Data collection

Diffraction	Mean temperature: 95 K
Diffraction source	Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.979334
Detector	Type: MAR CCD 165 mm / Detector: CCD / Date: Sep 23, 2004
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.979334 Å / Relative weight: 1
Reflection	Resolution: 2.45→32.59 Å / Num. obs: 54304 / % possible obs: 88.6 % / R_merge(I) obs: 0.077

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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: 2.45→32.59 Å / SU ML: 0.32 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 25.03 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.23	5489	10.11 %
R_work	0.186	-	-
obs	0.191	54304	88.6 %

Solvent computation

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

Displacement parameters

B_iso mean: 60.17 Å²

Refinement step

Cycle: LAST / Resolution: 2.45→32.59 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	8925	0	120	87	9132

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.008	9290
X-RAY DIFFRACTION	f_angle_d	1.044	12640
X-RAY DIFFRACTION	f_dihedral_angle_d	16.406	5430
X-RAY DIFFRACTION	f_chiral_restr	0.065	1371
X-RAY DIFFRACTION	f_plane_restr	0.007	1617

Refine LS restraints NCS

Ens-ID	Dom-ID	Auth asym-ID	Number	Refine-ID	Type
1	1	A	5397	X-RAY DIFFRACTION	POSITIONAL
1	2	B	5397	X-RAY DIFFRACTION	POSITIONAL
1	3	C	5397	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 (%)
2.4502-2.478	0.3024	31	0.2437	352	X-RAY DIFFRACTION	19
2.478-2.5072	0.3207	148	0.261	1222	X-RAY DIFFRACTION	67
2.5072-2.5378	0.2901	207	0.246	1755	X-RAY DIFFRACTION	98
2.5378-2.5699	0.2763	173	0.2426	1851	X-RAY DIFFRACTION	99
2.5699-2.6037	0.305	222	0.2457	1784	X-RAY DIFFRACTION	99
2.6037-2.6393	0.3204	209	0.2406	1803	X-RAY DIFFRACTION	99
2.6393-2.677	0.3043	190	0.2444	1798	X-RAY DIFFRACTION	99
2.677-2.7169	0.2856	199	0.2409	1833	X-RAY DIFFRACTION	99
2.7169-2.7594	0.2892	199	0.2461	1815	X-RAY DIFFRACTION	98
2.7594-2.8046	0.3103	203	0.2484	1769	X-RAY DIFFRACTION	98
2.8046-2.8529	0.3419	206	0.2423	1853	X-RAY DIFFRACTION	99
2.8529-2.9048	0.28	206	0.2297	1756	X-RAY DIFFRACTION	98
2.9048-2.9606	0.2747	199	0.2315	1794	X-RAY DIFFRACTION	98
2.9606-3.021	0.2901	218	0.2301	1785	X-RAY DIFFRACTION	98
3.021-3.0866	0.2634	188	0.2232	1810	X-RAY DIFFRACTION	98
3.0866-3.1584	0.2818	196	0.2253	1816	X-RAY DIFFRACTION	98
3.1584-3.2373	0.2776	207	0.232	1788	X-RAY DIFFRACTION	98
3.2373-3.3247	0.2721	209	0.2364	1778	X-RAY DIFFRACTION	98
3.3247-3.4225	0.2885	177	0.2135	1810	X-RAY DIFFRACTION	98
3.4225-3.5328	0.2558	212	0.2141	1756	X-RAY DIFFRACTION	95
3.5328-3.6589	0.3019	65	0.2112	553	X-RAY DIFFRACTION	30
3.6589-3.8052	0.2981	109	0.2493	840	X-RAY DIFFRACTION	47
3.8052-3.9781	0.196	140	0.1539	1072	X-RAY DIFFRACTION	59
3.9781-4.1874	0.1833	216	0.1545	1744	X-RAY DIFFRACTION	95
4.1874-4.4492	0.1745	200	0.1298	1745	X-RAY DIFFRACTION	96
4.4492-4.7917	0.1442	203	0.1182	1782	X-RAY DIFFRACTION	96
4.7917-5.2721	0.1802	208	0.1331	1767	X-RAY DIFFRACTION	96
5.2721-6.0308	0.1992	192	0.1599	1780	X-RAY DIFFRACTION	96
6.0308-7.5824	0.2091	184	0.1713	1799	X-RAY DIFFRACTION	95
7.5824-32.5925	0.1875	173	0.1753	1805	X-RAY DIFFRACTION	94

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	0.6593	-0.1743	0.014	1.0663	-0.5867	1.2612	-0.0837	0.0604	0.1176	0.059	-0.0087	-0.036	-0.1588	0.1447	0	0.3767	-0.0111	-0.0157	0.3494	0.0098	0.2604	39.9673	5.0993	16.8538
2	0.6783	0.4014	-0.1996	0.7812	-0.5231	0.9079	0.055	-0.0746	-0.0111	0.13	0.1531	0.5215	-0.3058	-0.1024	0.0013	0.4689	0.0887	0.0868	0.4041	0.0426	0.501	19.433	-4.8034	28.1447
3	0.7879	0.0668	0.1402	0.9883	-0.383	0.4391	-0.0853	0.1118	0.0113	-0.0533	0.0862	0.2275	-0.0432	-0.0662	0	0.465	0.0593	0.0263	0.3854	0.0021	0.3823	31.0779	-8.9655	24.4159
4	1.7626	0.2573	-0.1024	0.7664	0.0837	1.3484	0.013	-0.1416	-0.2099	-0.058	-0.043	0.0188	0.0862	-0.2548	0.0001	0.379	-0.0083	-0.0483	0.4155	0.0359	0.3621	16.5801	14.4801	-12.7789
5	1.0106	-0.0775	0.0635	0.4713	-0.2794	0.9686	-0.0036	0.1156	-0.7124	-0.1735	-0.0263	-0.1519	0.345	0.2042	-0.0113	0.4868	0.0306	0.0519	0.2447	-0.0321	0.7542	34.2871	-0.5705	-23.0914
6	1.4903	0.4616	-0.1948	0.2399	0.0114	0.5526	-0.0557	0.0969	-0.2833	0.063	0.0061	-0.0789	0.0174	0.1036	0.0001	0.4444	-0.0088	-0.0102	0.3448	0.0193	0.4816	33.1053	11.904	-19.943
7	0.6677	0.3485	-0.3335	1.1028	-0.3108	1.2325	0.0701	-0.0478	-0.0333	0.003	-0.0316	0.057	0.1285	-0.1135	-0	0.4005	0.0495	-0.0409	0.3936	0.0243	0.4367	8.7336	-48.6771	41.3439
8	0.6242	-0.0182	0.1651	0.8806	-0.7546	1.3488	0.1027	-0.0759	0.1649	0.2995	0.0956	0.1228	-0.3325	-0.1242	0.0008	0.4096	0.0324	0.1011	0.4813	-0.0205	0.5317	11.381	-23.5883	42.5185
9	0.63	0.5781	-0.4458	0.7598	-0.0575	0.9578	0.0362	-0.0612	-0.0446	0.0122	-0.056	0.1266	-0.0762	0.0448	0.0006	0.384	0.0773	-0.0038	0.4284	0.0183	0.4591	18.2679	-35.2418	32.8229

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 316 )
3	X-RAY DIFFRACTION	3	CHAIN 'A' AND (RESID 317 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 316 )
6	X-RAY DIFFRACTION	6	CHAIN 'B' AND (RESID 317 THROUGH 385 )
7	X-RAY DIFFRACTION	7	CHAIN 'C' AND (RESID -2 THROUGH 233 )
8	X-RAY DIFFRACTION	8	CHAIN 'C' AND (RESID 234 THROUGH 327 )
9	X-RAY DIFFRACTION	9	CHAIN 'C' AND (RESID 328 THROUGH 385 )

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