PDB-5qcx: Crystal structure of BACE complex with BMC007

ID or keywords:

Entry

Database: PDB / ID: 5qcx

Title

Crystal structure of BACE complex with BMC007

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 / amyloid-beta metabolic process ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT /

molecular replacement / Resolution: 2.2 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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PDBx/mmCIF format	5qcx.cif.gz	456.8 KB	Display	PDBx/mmCIF format
PDB format	pdb5qcx.ent.gz	390.1 KB	Display	PDB format
PDBx/mmJSON format	5qcx.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/qc/5qcx ftp://data.pdbj.org/pub/pdb/validation_reports/qc/5qcx	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	5qd7-1 3qbh-3 4acx-d 2xfk-d 5qcz-1 5qd6-1 2wf0-d 4zsq-2 2f3f-2 3pi5-2 3ixk-2 4b1d-d 3pi5-3 3k5f-2 2hiz-2 4gmi-d 3dm6-1 3zki-2 3skg-4 2fdp-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)	82.499, 104.052, 100.234
Angle α, β, γ (deg.)	90.00, 103.90, 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-E5D / (9R,11S)-3-ethyl-11-[(1R)-1-hydroxy-2-({[3-(propan-2-yl)phenyl]methyl}amino)ethyl]-9-methyl-3,12-diazabicyclo[12.3.1]octadeca-1(18),14,16-triene-2,13-dione Mass: 507.707 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₃₁H₄₅N₃O₃
#3: Water	ChemComp-HOH / water / Water Mass: 18.015 Da / Num. of mol.: 254 / 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: 3.11 Å³/Da / Density % sol: 60.44 %
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 3.8- ...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 3.8-FOLD EXCESS OF BMC007 ADDED FROM A 50MM STOCK SOLUTION IN DMSO (1.4% DMSO IN DROP). CRYO-PROTECTANT WAS 20%(V/V) 1,2-PROPANEDIOL, 80% (V/V) RESERVOIR SOLUTION.

Crystal

Density Matthews: 3.11 Å³/Da / Density % sol: 60.44 %

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 3.8- ...

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Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.97893
Detector	Type: MAR CCD 165 mm / Detector: CCD / Date: Jul 22, 2004
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97893 Å / Relative weight: 1
Reflection	Resolution: 2.2→55.623 Å / Num. obs: 83347 / % possible obs: 99.9 % / R_merge(I) obs: 0.069

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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: 2.2→55.62 Å / SU ML: 0.23 / Cross valid method: THROUGHOUT / σ(F): 1.38 / Phase error: 20.41 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.208	4227	5.07 %
R_work	0.178	-	-
obs	0.179	83347	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: 55.82 Å²

Refinement step

Cycle: LAST / Resolution: 2.2→55.62 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	8925	0	111	254	9290

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.007	9281
X-RAY DIFFRACTION	f_angle_d	0.921	12619
X-RAY DIFFRACTION	f_dihedral_angle_d	15.065	5421
X-RAY DIFFRACTION	f_chiral_restr	0.061	1365
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	5398	X-RAY DIFFRACTION	POSITIONAL
1	2	B	5398	X-RAY DIFFRACTION	POSITIONAL
1	3	C	5398	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 (%)
2.2-2.225	0.2439	147	0.1862	2599	X-RAY DIFFRACTION	97
2.225-2.2512	0.2163	148	0.1905	2583	X-RAY DIFFRACTION	100
2.2512-2.2787	0.2386	118	0.1836	2666	X-RAY DIFFRACTION	100
2.2787-2.3075	0.2231	153	0.1877	2607	X-RAY DIFFRACTION	100
2.3075-2.3379	0.2046	134	0.1798	2625	X-RAY DIFFRACTION	100
2.3379-2.3699	0.2394	150	0.1832	2647	X-RAY DIFFRACTION	100
2.3699-2.4038	0.2214	121	0.1921	2625	X-RAY DIFFRACTION	100
2.4038-2.4397	0.2351	165	0.1926	2612	X-RAY DIFFRACTION	100
2.4397-2.4778	0.21	141	0.191	2620	X-RAY DIFFRACTION	100
2.4778-2.5184	0.2366	137	0.1894	2641	X-RAY DIFFRACTION	100
2.5184-2.5618	0.2309	137	0.1856	2632	X-RAY DIFFRACTION	100
2.5618-2.6084	0.2288	133	0.1904	2642	X-RAY DIFFRACTION	100
2.6084-2.6586	0.2757	144	0.1963	2643	X-RAY DIFFRACTION	100
2.6586-2.7128	0.2355	147	0.2001	2603	X-RAY DIFFRACTION	100
2.7128-2.7718	0.2407	133	0.1974	2633	X-RAY DIFFRACTION	100
2.7718-2.8363	0.2427	152	0.2072	2645	X-RAY DIFFRACTION	100
2.8363-2.9072	0.225	147	0.21	2618	X-RAY DIFFRACTION	100
2.9072-2.9858	0.242	147	0.2106	2615	X-RAY DIFFRACTION	100
2.9858-3.0737	0.243	126	0.2014	2676	X-RAY DIFFRACTION	100
3.0737-3.1729	0.2765	139	0.2158	2644	X-RAY DIFFRACTION	100
3.1729-3.2863	0.2393	138	0.212	2629	X-RAY DIFFRACTION	100
3.2863-3.4178	0.2015	128	0.2027	2666	X-RAY DIFFRACTION	100
3.4178-3.5734	0.235	143	0.1914	2637	X-RAY DIFFRACTION	100
3.5734-3.7617	0.2105	141	0.1753	2634	X-RAY DIFFRACTION	100
3.7617-3.9973	0.1938	156	0.1547	2623	X-RAY DIFFRACTION	100
3.9973-4.3059	0.1733	138	0.1502	2663	X-RAY DIFFRACTION	100
4.3059-4.739	0.1444	123	0.1287	2678	X-RAY DIFFRACTION	100
4.739-5.4242	0.1745	163	0.1452	2631	X-RAY DIFFRACTION	100
5.4242-6.832	0.2067	151	0.1752	2669	X-RAY DIFFRACTION	100
6.832-55.6407	0.1914	127	0.1806	2714	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	0.95	0.1788	0.1091	2.2074	-0.5433	0.9694	-0.0632	0.1855	0.1042	0.0292	0.007	-0.0078	-0.1559	0.1846	-0	0.3936	-0.0039	-0.0157	0.4184	0.0066	0.2772	40.0477	4.9508	16.9366
2	0.8681	-0.0818	-0.0127	1.3119	-1.0932	1.2368	0.0074	0.1615	-0.0222	0.2807	0.1744	0.5023	-0.3773	-0.1268	0.0416	0.4473	0.0959	0.0998	0.3262	0.0284	0.4652	20.2381	-3.6722	27.5063
3	0.4211	-0.0247	0.2994	1.0196	-0.6451	0.5759	0.0154	0.1047	-0.1497	0.0436	0.0191	0.1862	-0.0716	-0.0307	0	0.3975	0.0444	0.0429	0.4112	-0.034	0.3562	34.5293	-13.0756	24.6666
4	2.5985	0.4772	0.0309	0.8298	0.236	1.8787	0.0167	-0.1351	-0.2736	0.0679	-0.0526	0.0242	0.0293	-0.3359	-0	0.3491	-0.0256	-0.0155	0.3806	0.0512	0.3664	16.9635	14.039	-12.8738
5	1.7013	-0.3008	0.7188	0.8162	-0.1647	0.8948	0.1742	0.3312	-0.8555	-0.2235	-0.0275	-0.4593	0.2127	0.1529	0.0553	0.3836	0.0168	-0.008	0.2367	-0.1122	0.6939	34.8392	-1.3402	-22.7375
6	2.1357	0.4114	-0.1167	0.4158	0.081	0.3534	0.0857	0.1526	-0.4445	0.0658	-0.0747	-0.1783	-0.0168	0.118	0.0007	0.3642	0.001	-0.0207	0.3104	0.0209	0.4267	33.5963	11.7762	-20.0096
7	0.4322	0.2179	-0.5382	0.2197	-0.2484	0.6845	0.1136	0.0767	-0.0671	-0.084	-0.0511	0.0139	0.1357	-0.2887	-0.0002	0.3997	0.0132	-0.0387	0.4127	0.0079	0.4665	0.5515	-49.3923	38.9596
8	1.1127	1.0191	0.0249	1.4849	-0.3201	1.4426	0.1411	-0.165	-0.1709	0.1691	-0.0986	0.0177	0.3723	-0.1405	-0.0001	0.4547	0.0076	-0.0526	0.3662	0.046	0.4277	4.8707	-55.6792	47.6026
9	0.2398	0.2334	-0.1607	0.2394	-0.2567	0.5658	-0.0059	0.0154	0.176	-0.0394	0.1631	-0.0909	0.2288	-0.2216	0.0002	0.4119	0.0544	-0.0447	0.3957	-0.0191	0.3903	4.9284	-44.6588	31.5971
10	1.2646	-0.1156	-0.3146	1.4773	-0.8522	1.6986	0.2032	-0.0822	0.0239	0.2542	0.0008	-0.1368	-0.2114	0.0834	0.0162	0.3512	0.0368	0.0342	0.3866	-0.0013	0.3928	16.8681	-29.3708	41.1027
11	0.6274	0.2565	0.3357	1.0734	-0.8375	1.1347	0.1059	-0.0253	0.183	0.0982	0.2084	0.0697	-0.122	-0.2187	0.0115	0.3259	0.0581	0.0637	0.3915	0.043	0.4151	10.8123	-25.9878	38.6381
12	0.6029	0.8224	-0.2685	1.147	-0.2154	1.1461	0.0076	0.0143	-0.1418	0.0325	-0.0857	-0.1053	0.0001	0.0957	-0.0002	0.3211	0.0924	0.0038	0.3791	0.0052	0.4133	17.7199	-35.022	32.9044

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 317 )
6	X-RAY DIFFRACTION	6	CHAIN 'B' AND (RESID 318 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 143 )
9	X-RAY DIFFRACTION	9	CHAIN 'C' AND (RESID 144 THROUGH 176 )
10	X-RAY DIFFRACTION	10	CHAIN 'C' AND (RESID 177 THROUGH 276 )
11	X-RAY DIFFRACTION	11	CHAIN 'C' AND (RESID 277 THROUGH 327 )
12	X-RAY DIFFRACTION	12	CHAIN 'C' AND (RESID 328 THROUGH 385 )

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