PDB-5qd7: Crystal structure of BACE complex with BMC014

ID or keywords:

Entry

Database: PDB / ID: 5qd7

Title

Crystal structure of BACE complex with BMC014

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: 2.12 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: Derived calculations / Structure summary Category: audit_author / chem_comp ...audit_author / chem_comp / entity / pdbx_entity_nonpoly Item: _audit_author.identifier_ORCID / _chem_comp.name ..._audit_author.identifier_ORCID / _chem_comp.name / _entity.pdbx_description / _pdbx_entity_nonpoly.name
Revision 1.2	Feb 10, 2021	Group: Database references / Category: citation_author / Item: _citation_author.identifier_ORCID

Structure viewer	Molecule: MolmilJmol/JSmol

-
Download

PDBx/mmCIF format	5qd7.cif.gz	458.4 KB	Display	PDBx/mmCIF format
PDB format	pdb5qd7.ent.gz	391.4 KB	Display	PDB format
PDBx/mmJSON format	5qd7.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

-
Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/qd/5qd7 ftp://data.pdbj.org/pub/pdb/validation_reports/qd/5qd7	HTTPS FTP

-
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

-
Related structure data

Similar structure data	5qd2-3 2wf2-d 2xfk-d 5qcw-3 5qd6-1 5qd2-1 5qcz-1 5qcx-1 2f3f-2 5qcx-2 2xfi-d 2wf0-d 3pi5-2 5qco-1 2wf4-d 5qcv-2 4k8s-2 5qcs-2 4b1d-d 4lxa-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

-
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)	81.752, 103.186, 100.144
Angle α, β, γ (deg.)	90.00, 104.44, 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-0BI / (4S)-4-[(1R)-1-hydroxy-2-({1-[3-(1-methylethyl)phenyl]cyclopropyl}amino)ethyl]-19-(methoxymethyl)-11-oxa-3,16-diazatric yclo[15.3.1.1~6,10~]docosa-1(21),6(22),7,9,17,19-hexaen-2-one / (S)-4-{(R)-1-Hydroxy-2-[1-(3-isopropyl-phenyl)-cyclopropylamino]-ethyl}-19-methoxymethyl-11-oxa 3,16-diaza-tricyclo[15.3.1.16,10]docosa-1(21),6,8,10(22),17 ,19-hexaen-2-one Mass: 571.749 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₃₅H₄₅N₃O₄
#3: Water	ChemComp-HOH / water / Water Mass: 18.015 Da / Num. of mol.: 290 / Source method: isolated from a natural source / Formula: H₂O

-
Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

Crystal	Density Matthews: 3.05 Å³/Da / Density % sol: 59.61 %
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 BMC014 ADDED FROM A 50MM STOCK SOLUTION IN 90% DMSO-D6 (1.7% DMSO IN DROP). A SOLUTION CONTAINING 1.2M AMMONIUM SULFATE, 25% (V/V) GLYCEROL, 1.0MM BMC014 WAS USED AS CRYO-PROTECTANT.

Crystal

Density Matthews: 3.05 Å³/Da / Density % sol: 59.61 %

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 ...

-
Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.97945
Detector	Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Aug 25, 2006
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97945 Å / Relative weight: 1
Reflection	Resolution: 2.12→58.239 Å / Num. obs: 91075 / % possible obs: 99.8 % / R_merge(I) obs: 0.048

-
Phasing

Phasing	Method: molecular replacement

-
Processing

Software

Name	Version	Classification
PHENIX	1.12_2829	refinement
CNX		refinement
CNX		phasing
XSCALE		data scaling
XDS		date reduction
PDB_EXTRACT	3.24	data extraction

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.12→58.24 Å / SU ML: 0.2 / Cross valid method: THROUGHOUT / σ(F): 1.38 / Phase error: 18.55 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.188	9102	9.99 %
R_work	0.165	-	-
obs	0.167	91075	99.8 %

Solvent computation

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

Displacement parameters

B_iso mean: 53.04 Å²

Refinement step

Cycle: LAST / Resolution: 2.12→58.24 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	8925	0	126	290	9341

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.007	9302
X-RAY DIFFRACTION	f_angle_d	0.885	12655
X-RAY DIFFRACTION	f_dihedral_angle_d	14.674	5430
X-RAY DIFFRACTION	f_chiral_restr	0.059	1365
X-RAY DIFFRACTION	f_plane_restr	0.005	1620

Refine LS restraints NCS

Ens-ID	Dom-ID	Auth asym-ID	Number	Refine-ID	Type
1	1	A	5430	X-RAY DIFFRACTION	POSITIONAL
1	2	B	5430	X-RAY DIFFRACTION	POSITIONAL
1	3	C	5430	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 (%)
2.12-2.1441	0.2646	301	0.2288	2733	X-RAY DIFFRACTION	100
2.1441-2.1693	0.2677	310	0.2172	2704	X-RAY DIFFRACTION	100
2.1693-2.1958	0.2251	283	0.195	2754	X-RAY DIFFRACTION	100
2.1958-2.2236	0.2146	311	0.1886	2725	X-RAY DIFFRACTION	100
2.2236-2.2529	0.2318	287	0.1855	2732	X-RAY DIFFRACTION	100
2.2529-2.2837	0.2302	331	0.1793	2699	X-RAY DIFFRACTION	100
2.2837-2.3163	0.226	306	0.1888	2714	X-RAY DIFFRACTION	100
2.3163-2.3509	0.2658	287	0.1921	2779	X-RAY DIFFRACTION	100
2.3509-2.3877	0.2226	302	0.1921	2726	X-RAY DIFFRACTION	100
2.3877-2.4268	0.2457	284	0.1896	2703	X-RAY DIFFRACTION	100
2.4268-2.4687	0.2349	339	0.1804	2715	X-RAY DIFFRACTION	100
2.4687-2.5135	0.2045	288	0.176	2733	X-RAY DIFFRACTION	100
2.5135-2.5619	0.2108	314	0.1728	2749	X-RAY DIFFRACTION	100
2.5619-2.6142	0.2174	327	0.1735	2698	X-RAY DIFFRACTION	100
2.6142-2.671	0.198	296	0.1768	2737	X-RAY DIFFRACTION	100
2.671-2.7332	0.2014	310	0.1806	2721	X-RAY DIFFRACTION	100
2.7332-2.8015	0.2099	314	0.1848	2722	X-RAY DIFFRACTION	100
2.8015-2.8773	0.2122	285	0.1864	2767	X-RAY DIFFRACTION	100
2.8773-2.9619	0.2214	295	0.181	2721	X-RAY DIFFRACTION	100
2.9619-3.0575	0.204	305	0.176	2749	X-RAY DIFFRACTION	100
3.0575-3.1668	0.2072	284	0.1828	2746	X-RAY DIFFRACTION	100
3.1668-3.2936	0.2192	285	0.1805	2751	X-RAY DIFFRACTION	100
3.2936-3.4434	0.19	324	0.1725	2725	X-RAY DIFFRACTION	100
3.4434-3.625	0.1797	296	0.1595	2735	X-RAY DIFFRACTION	100
3.625-3.852	0.1688	291	0.1483	2775	X-RAY DIFFRACTION	100
3.852-4.1494	0.1533	311	0.141	2722	X-RAY DIFFRACTION	100
4.1494-4.5668	0.1458	314	0.1294	2749	X-RAY DIFFRACTION	100
4.5668-5.2273	0.1349	320	0.1306	2746	X-RAY DIFFRACTION	100
5.2273-6.5844	0.1855	319	0.1658	2765	X-RAY DIFFRACTION	100
6.5844-58.2607	0.1902	283	0.1768	2678	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	1.0577	0.0242	0.2144	2.0031	-0.2688	1.1189	-0.0775	0.1589	0.1488	-0.0682	0.0176	-0.0561	-0.2058	0.0926	0.0001	0.3635	-0.0067	-0.0119	0.3013	0.0274	0.2244	39.9594	4.8177	16.9099
2	1.0453	-0.0918	-0.0855	0.6182	-0.8672	1.2591	0.0034	0.1668	0.0708	0.2317	0.1369	0.3599	-0.4481	-0.1072	0.1078	0.4527	0.0941	0.0768	0.2607	0.0372	0.3966	19.5341	-3.5105	27.1158
3	0.4796	-0.4117	0.157	0.8705	-0.4286	0.3894	0.038	0.0303	-0.1568	-0.0771	-0.0502	0.1798	-0.1296	-0.1008	-0.0001	0.3754	0.0275	0.044	0.3532	-0.0199	0.3023	33.8354	-13.0071	24.5596
4	2.1635	0.5682	0.3652	1.0761	0.1542	1.6955	0.0799	-0.2022	-0.2679	0.0549	-0.0599	0.0688	-0.0015	-0.3642	-0.0004	0.268	-0.0068	-0.0203	0.3456	0.0554	0.289	17.0969	13.8999	-12.6241
5	1.1593	-0.316	0.3556	0.4009	0.031	1.4455	0.1224	0.2638	-0.8237	-0.1826	-0.0228	-0.2984	0.4162	0.0194	0.0827	0.4	-0.0115	-0.0382	0.1958	-0.0812	0.6802	33.5033	-0.9888	-22.5355
6	1.2942	0.7973	0.0957	0.6161	0.1863	0.3196	0.0153	0.192	-0.3229	0.0622	-0.0025	-0.127	-0.0839	0.0838	-0.0007	0.3132	0.0263	-0.0154	0.3105	0.034	0.3712	36.0978	15.8474	-19.4166
7	0.8776	-0.0744	-0.2192	1.2569	-0.1798	2.0816	-0.005	-0.0866	-0.1631	0.1235	-0.0199	0.0922	0.3471	-0.345	-0.0002	0.3465	-0.057	-0.0185	0.3977	0.0683	0.4481	2.905	-53.7498	44.7117
8	0.2367	0.1887	-0.0253	0.244	-0.2182	0.4049	-0.0491	0.2283	-0.0416	-0.0074	0.087	0.1651	0.2636	-0.5089	-0.0001	0.346	0.0101	-0.0312	0.4046	0.0147	0.3745	4.4649	-44.4653	31.1918
9	0.948	-0.2061	-0.636	0.9661	-0.4001	0.7417	0.14	-0.1671	-0.0173	0.1307	0.0065	-0.0943	-0.0884	0.0633	-0.0001	0.3174	0.0138	0.0027	0.3819	0.0088	0.3799	19.8549	-33.0879	38.8647
10	0.2527	0.322	0.1233	1.2358	-0.5926	0.9289	0.1955	-0.001	0.2323	0.2286	0.2708	0.1898	-0.2232	-0.285	0.2057	0.3241	0.1163	0.1608	0.3806	0.1277	0.4183	8.4288	-22.5647	41.3639
11	0.4049	0.4483	-0.2621	0.7132	0.0309	0.9906	0.1197	-0.1002	-0.0688	-0.0155	-0.0603	-0.0023	-0.0901	-0.0441	0.0009	0.3287	0.0551	-0.0043	0.3698	0.0293	0.386	17.1108	-34.7447	32.8049

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 143 )
8	X-RAY DIFFRACTION	8	CHAIN 'C' AND (RESID 144 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 327 )
11	X-RAY DIFFRACTION	11	CHAIN 'C' AND (RESID 328 THROUGH 385 )

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

Version 3 of the EMDB header file is now the official format.
The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi

Thousand views of thousand structures

Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

-
Movie

-
Structure viewers

+
Viewer log

-
This page

-
This web site

-
Options

+
Open data

-
Basic information

-
Structure visualization

-
Downloads & links

-
Download

-
Validation report

-
Group deposition

-
Related structure data

-
Links

-
Assembly

-
Components

-
Experimental details

-
Experiment

-
Sample preparation

-
Data collection

-
Phasing

-
Processing

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

-
Aug 12, 2020. Covid-19 info

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi

-Movie

-Structure viewers

+Viewer log

-This page

-This web site

-Options

+Open data

-Basic information

-Structure visualization

-Downloads & links

-Download

-Validation report

-Group deposition

-Related structure data

-Links

-Assembly

-Components

-Experimental details

-Experiment

-Sample preparation

-Data collection

-Phasing

-Processing

+About Yorodumi

-News

-Feb 9, 2022. New format data for meta-information of EMDB entries

-Aug 12, 2020. Covid-19 info

+Mar 5, 2020. Novel coronavirus structure data

+Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+Jul 12, 2017. Major update of PDB

-Yorodumi

-
Movie

-
Structure viewers

+
Viewer log

-
This page

-
This web site

-
Options

+
Open data

-
Basic information

-
Structure visualization

-
Downloads & links

-
Download

-
Validation report

-
Group deposition

-
Related structure data

-
Links

-
Assembly

-
Components

-
Experimental details

-
Experiment

-
Sample preparation

-
Data collection

-
Phasing

-
Processing

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

-
Aug 12, 2020. Covid-19 info

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi