PDB-5qd4: Crystal structure of BACE complex with BMC023

ID or keywords:

Entry

Database: PDB / ID: 5qd4

Title

Crystal structure of BACE complex with BMC023

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 /

prepulse inhibition / detection of mechanical stimulus involved in sensory perception of pain ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT /

molecular replacement / Resolution: 2.112 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

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	5qd4.cif.gz	460.4 KB	Display	PDBx/mmCIF format
PDB format	pdb5qd4.ent.gz	393.7 KB	Display	PDB format
PDBx/mmJSON format	5qd4.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/qd/5qd4 ftp://data.pdbj.org/pub/pdb/validation_reports/qd/5qd4	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	3k5f-1 5qcz-1 3dv1-1 4gmi-d 5qcp-2 2g94-1 2p8h-d 5qd7-1 6uwv-1 2xfk-d 5ygy-d 5qd9-1 5qdb-3 5qd8-3 2vkm-4 2p4j-2 3cid-1 5qd6-1 5qd2-3 3k5f-3 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
45.5 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Beta-secretase 1

hetero molecules

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

3

C: Beta-secretase 1

hetero molecules

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

Unit cell

Length a, b, c (Å)	82.244, 103.781, 100.961
Angle α, β, γ (deg.)	90.00, 103.04, 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-AXQ / {(E)-(3R,6S,9R)-3-[(1S,3R)-3-((S)-1 -BUTYLCARBAMOYL-2-METHYL-PROPYLCARB AMOYL)-1-HYDROXY-BUTYL]-6-METHYL-5, 8-DIOXO-1,11-DITHIA-4,7-DIAZA-CYCLO PENTADEC-13-EN-9-YL}-CARBAMIC ACID TERT-BUTYL ESTER Mass: 673.928 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₃₁H₅₅N₅O₇S₂
#3: Water	ChemComp-HOH / water / Water Mass: 18.015 Da / Num. of mol.: 219 / 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: 3.12 Å³/Da / Density % sol: 60.64 %
Crystal grow	Temperature: 292 K / Method: hanging drop 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 XII 8.45MG/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 XII 8.45MG/ML IN 10MM TRIS-HCL PH 7.4, 25MM NACL, WITH A 2.5-FOLD EXCESS OF BMC023 ADDED FROM A 25MM STOCK SOLUTION IN DMSO (2% DMSO IN DROP). CRYO-PROTECTANT WAS 1.2M AMMONIUM PHOSPHATE, 0.1M SODIUM CITRATE PH 5.0, 25% GLYCEROL, 0.5MM BMC023, 2% DMSO.

Crystal

Density Matthews: 3.12 Å³/Da / Density % sol: 60.64 %

Crystal grow

Temperature: 292 K / Method: hanging drop
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 XII 8.45MG/ML IN 10MM TRIS-HCL ...

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Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.9784
Detector	Detector: CCD / Date: Dec 3, 2004
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.9784 Å / Relative weight: 1
Reflection	Resolution: 2.112→56.219 Å / Num. obs: 93651 / % possible obs: 98.87 % / R_merge(I) obs: 0.065

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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: 2.112→56.219 Å / SU ML: 0.2 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 19.61 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.203	4701	5.02 %
R_work	0.169	-	-
obs	0.1707	93652	98.87 %

Solvent computation

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

Refinement step

Cycle: LAST / Resolution: 2.112→56.219 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	8925	0	135	219	9279

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.007	9296
X-RAY DIFFRACTION	f_angle_d	0.792	12637
X-RAY DIFFRACTION	f_dihedral_angle_d	15.046	5409
X-RAY DIFFRACTION	f_chiral_restr	0.056	1374
X-RAY DIFFRACTION	f_plane_restr	0.005	1623

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 (%)
2.1121-2.1361	0.2682	125	0.2182	2324	X-RAY DIFFRACTION	79
2.1361-2.1612	0.2516	152	0.1988	3029	X-RAY DIFFRACTION	100
2.1612-2.1876	0.2122	144	0.1916	2975	X-RAY DIFFRACTION	100
2.1876-2.2152	0.2335	132	0.1883	3020	X-RAY DIFFRACTION	100
2.2152-2.2444	0.2245	162	0.1807	2992	X-RAY DIFFRACTION	100
2.2444-2.2751	0.2176	162	0.175	2966	X-RAY DIFFRACTION	100
2.2751-2.3077	0.2095	135	0.1788	3017	X-RAY DIFFRACTION	100
2.3077-2.3421	0.2377	153	0.177	2986	X-RAY DIFFRACTION	100
2.3421-2.3787	0.2331	162	0.1781	2952	X-RAY DIFFRACTION	100
2.3787-2.4177	0.2338	160	0.1851	3027	X-RAY DIFFRACTION	100
2.4177-2.4594	0.1987	152	0.1783	3004	X-RAY DIFFRACTION	100
2.4594-2.5041	0.2273	167	0.1705	2968	X-RAY DIFFRACTION	100
2.5041-2.5523	0.1874	160	0.1713	2978	X-RAY DIFFRACTION	100
2.5523-2.6044	0.1972	191	0.1738	2952	X-RAY DIFFRACTION	100
2.6044-2.661	0.2604	174	0.1811	2997	X-RAY DIFFRACTION	100
2.661-2.7229	0.2507	185	0.1859	2962	X-RAY DIFFRACTION	100
2.7229-2.791	0.2253	162	0.1895	2967	X-RAY DIFFRACTION	100
2.791-2.8664	0.2189	162	0.1866	3000	X-RAY DIFFRACTION	100
2.8664-2.9508	0.2095	177	0.1845	3003	X-RAY DIFFRACTION	100
2.9508-3.046	0.2195	151	0.1823	2992	X-RAY DIFFRACTION	100
3.046-3.1549	0.2432	156	0.1841	3012	X-RAY DIFFRACTION	100
3.1549-3.2812	0.2119	130	0.1951	3033	X-RAY DIFFRACTION	100
3.2812-3.4305	0.224	165	0.1868	2964	X-RAY DIFFRACTION	100
3.4305-3.6113	0.2207	139	0.1663	3041	X-RAY DIFFRACTION	100
3.6113-3.8375	0.182	149	0.1597	2989	X-RAY DIFFRACTION	100
3.8375-4.1338	0.1908	148	0.1461	3028	X-RAY DIFFRACTION	100
4.1338-4.5496	0.1691	163	0.1381	2940	X-RAY DIFFRACTION	98
4.5496-5.2075	0.157	150	0.1364	2883	X-RAY DIFFRACTION	96
5.2075-6.5593	0.1905	179	0.1715	3017	X-RAY DIFFRACTION	100
6.5593-56.2388	0.1964	154	0.178	2933	X-RAY DIFFRACTION	95

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	2.2223	-0.8253	0.5776	3.9529	-0.6104	2.3467	-0.1433	0.3399	0.5172	-0.007	-0.0435	-0.2957	-0.4583	0.2507	0.1362	0.4732	-0.108	-0.0345	0.434	0.0972	0.3729	43.4564	10.0407	16.5205
2	1.7881	-0.0074	-0.2492	2.5057	0.0585	1.9593	-0.0956	0.2754	-0.0211	-0.0193	0.1603	0.7345	-0.1238	-0.3032	-0.0454	0.3612	0.0564	-0.0238	0.354	0.0492	0.456	23.6158	-8.5529	20.427
3	2.0385	-0.0696	-0.0521	1.2469	-0.1696	2.0002	-0.1076	-0.037	0.3326	0.4048	0.0983	0.5039	-0.5572	-0.18	0.0384	0.5173	0.0953	0.0835	0.3285	0.026	0.4622	23.6324	-3.6306	29.2959
4	2.3794	0.3465	0.3057	2.6944	-0.983	0.9519	-0.0806	0.1104	-0.1757	-0.0441	0.1034	0.3204	-0.1585	-0.1453	-0.042	0.3528	0.0423	0.0181	0.3182	-0.0008	0.2594	34.6419	-13.0618	25.0607
5	3.8319	0.9877	0.2275	1.7468	0.0977	2.2689	0.0518	-0.2289	-0.5246	0.1459	-0.0114	0.0443	0.0436	-0.4748	-0.0118	0.2628	0.0172	-0.0258	0.3321	0.0619	0.3143	16.5918	13.6347	-13.4408
6	0.8553	-0.1584	0.2174	1.2214	0.1076	1.9069	-0.0338	0.3244	-1.3077	-0.0994	-0.0505	-0.5196	0.8869	0.034	0.0049	0.6465	-0.0047	0.074	0.3265	-0.1459	1.0907	33.2023	-1.0043	-23.5506
7	3.2205	0.3227	-1.0823	0.9538	0.8734	2.8304	-0.0511	0.204	-0.5985	-0.0972	-0.0111	-0.2086	0.1106	0.3079	-0.0836	0.2983	0.0075	-0.0133	0.3034	0.0231	0.4048	35.8213	15.8087	-20.0482
8	2.8295	0.6783	-0.9614	1.1102	-1.9766	3.8362	-0.0855	0.2534	0.0099	0.1207	-0.0689	0.1243	0.1618	-1.1118	0.2635	0.3228	-0.0169	-0.0176	0.5147	0.0029	0.4269	-1.2418	-48.2529	36.7675
9	1.6935	-0.2208	0.1907	1.0226	0.3015	2.5368	-0.0698	-0.2064	-0.1629	0.3565	0.0074	0.2924	0.4158	-0.5286	0.0664	0.5161	-0.0813	0.0455	0.4688	0.078	0.4601	2.0209	-55.1691	50.8201
10	2.1607	0.1686	-0.7125	1.9225	0.1254	3.954	-0.044	-0.0316	-0.2016	0.0796	-0.0118	0.0152	0.4573	-0.4077	0.059	0.3073	-0.0114	-0.0314	0.2958	0.039	0.3674	6.5745	-52.3051	42.5746
11	2.3986	0.2938	-0.6288	2.0597	-0.359	1.6978	0.1936	-0.2928	0.1699	0.2209	-0.0735	-0.2025	-0.2171	0.0994	-0.1267	0.3001	0.027	-0.006	0.3358	0.0107	0.3619	20.5437	-33.0127	39.7809
12	1.5427	0.2197	0.354	2.2573	-0.5919	2.0795	0.1334	-0.1636	0.2953	0.4828	0.0503	0.3163	-0.4038	-0.4755	-0.1295	0.4171	0.0996	0.1145	0.4261	0.0124	0.4325	9.702	-24.3979	42.0612
13	1.2239	1.3078	-0.8839	1.994	-0.0147	2.324	0.0179	-0.0788	0.0964	0.0155	0.0374	-0.0539	-0.1622	-0.0151	-0.0295	0.3247	0.0751	0.0072	0.3442	0.0448	0.3956	18.6601	-34.8492	31.5322

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	CHAIN 'A' AND (RESID -2 THROUGH 183 )
2	X-RAY DIFFRACTION	2	CHAIN 'A' AND (RESID 184 THROUGH 267 )
3	X-RAY DIFFRACTION	3	CHAIN 'A' AND (RESID 268 THROUGH 340 )
4	X-RAY DIFFRACTION	4	CHAIN 'A' AND (RESID 341 THROUGH 385 )
5	X-RAY DIFFRACTION	5	CHAIN 'B' AND (RESID -2 THROUGH 233 )
6	X-RAY DIFFRACTION	6	CHAIN 'B' AND (RESID 234 THROUGH 340 )
7	X-RAY DIFFRACTION	7	CHAIN 'B' AND (RESID 341 THROUGH 385 )
8	X-RAY DIFFRACTION	8	CHAIN 'C' AND (RESID -2 THROUGH 24 )
9	X-RAY DIFFRACTION	9	CHAIN 'C' AND (RESID 25 THROUGH 74 )
10	X-RAY DIFFRACTION	10	CHAIN 'C' AND (RESID 75 THROUGH 176 )
11	X-RAY DIFFRACTION	11	CHAIN 'C' AND (RESID 177 THROUGH 252 )
12	X-RAY DIFFRACTION	12	CHAIN 'C' AND (RESID 253 THROUGH 340 )
13	X-RAY DIFFRACTION	13	CHAIN 'C' AND (RESID 341 THROUGH 385 )

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