[English] 日本語
Yorodumi
- PDB-6e3z: Structure of Bace-1 in complex with Ligand 8 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6e3z
TitleStructure of Bace-1 in complex with Ligand 8
ComponentsBeta-secretase 1
KeywordsHYDROLASE/INHIBITOR / bace protease / hydrolase / HYDROLASE-INHIBITOR complex
Function / homology
Function and homology information


memapsin 2 / Golgi-associated vesicle lumen / beta-aspartyl-peptidase activity / signaling receptor ligand precursor processing / amyloid-beta formation / amyloid precursor protein catabolic process / membrane protein ectodomain proteolysis / amyloid-beta metabolic process / detection of mechanical stimulus involved in sensory perception of pain / prepulse inhibition ...memapsin 2 / Golgi-associated vesicle lumen / beta-aspartyl-peptidase activity / signaling receptor ligand precursor processing / amyloid-beta formation / amyloid precursor protein catabolic process / membrane protein ectodomain proteolysis / amyloid-beta metabolic process / detection of mechanical stimulus involved in sensory perception of pain / prepulse inhibition / cellular response to manganese ion / multivesicular body / presynaptic modulation of chemical synaptic transmission / protein serine/threonine kinase binding / cellular response to copper ion / hippocampal mossy fiber to CA3 synapse / trans-Golgi network / recycling endosome / protein processing / response to lead ion / cellular response to amyloid-beta / synaptic vesicle / late endosome / peptidase activity / positive regulation of neuron apoptotic process / amyloid-beta binding / endopeptidase activity / amyloid fibril formation / aspartic-type endopeptidase activity / early endosome / lysosome / endosome / endosome membrane / membrane raft / endoplasmic reticulum lumen / Amyloid fiber formation / axon / neuronal cell body / dendrite / enzyme binding / cell surface / Golgi apparatus / proteolysis / membrane / plasma membrane
Similarity search - Function
Beta-secretase BACE1 / Beta-secretase BACE / Memapsin-like / Eukaryotic aspartyl protease / Aspartic peptidase A1 family / Peptidase family A1 domain / Peptidase family A1 domain profile. / Cathepsin D, subunit A; domain 1 / Acid Proteases / Aspartic peptidase, active site ...Beta-secretase BACE1 / Beta-secretase BACE / Memapsin-like / Eukaryotic aspartyl protease / Aspartic peptidase A1 family / Peptidase family A1 domain / Peptidase family A1 domain profile. / Cathepsin D, subunit A; domain 1 / Acid Proteases / Aspartic peptidase, active site / Eukaryotic and viral aspartyl proteases active site. / Aspartic peptidase domain superfamily / Beta Barrel / Mainly Beta
Similarity search - Domain/homology
Chem-HRV / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.94 Å
AuthorsShaffer, P.L.
CitationJournal: Acs Symp.Ser. / Year: 2020
Title: Discovery and Chemical Development of JNJ-50138803, a Clinical Candidate BACE1 Inhibitor
Authors: Gijsen, H.J.M. / Lin, J. / Houpis, Y.
History
DepositionJul 16, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 11, 2019Provider: repository / Type: Initial release
Revision 1.1Mar 25, 2020Group: Database references / Category: citation
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.pdbx_database_id_DOI / _citation.title / _citation.year
Revision 1.2Oct 23, 2024Group: Advisory / Data collection ...Advisory / 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 / pdbx_unobs_or_zero_occ_atoms
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Beta-secretase 1
B: Beta-secretase 1
C: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)146,1947
Polymers144,3333
Non-polymers1,8614
Water14,772820
1
A: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)48,5762
Polymers48,1111
Non-polymers4651
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)48,5762
Polymers48,1111
Non-polymers4651
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,0423
Polymers48,1111
Non-polymers9302
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)232.178, 100.500, 63.968
Angle α, β, γ (deg.)90.000, 103.220, 90.000
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11A-629-

HOH

21A-692-

HOH

-
Components

#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: 48111.129 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-HRV / N-{3-[(2R,3R)-5-amino-3-methyl-2-(trifluoromethyl)-3,6-dihydro-2H-1,4-oxazin-3-yl]-4-fluorophenyl}-3,5-dichloropyridine-2-carboxamide


Mass: 465.229 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C18H14Cl2F4N4O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 820 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.52 Å3/Da / Density % sol: 51.13 %
Crystal growTemperature: 293 K / Method: vapor diffusion / pH: 6.25 / Details: 17% PEG-4000, 0.1 M MES

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.99986 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Oct 19, 2011
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99986 Å / Relative weight: 1
ReflectionResolution: 1.94→49.451 Å / Num. obs: 104486 / % possible obs: 98.8 % / Redundancy: 4.13 % / Biso Wilson estimate: 33.42 Å2 / Rmerge F obs: 0.096 / Rmerge(I) obs: 0.044 / Rrim(I) all: 0.051 / Χ2: 1.067 / Net I/σ(I): 18.16 / Num. measured all: 431560 / Scaling rejects: 204
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsRrim(I) all% possible all
1.94-2.144.1930.4053.7263820.46398.3
2.14-2.464.130.1767.92264520.20299
2.46-34.2010.07117.14230400.08199
3-3.84.0810.03332.62144670.03799
3.8-4.883.8180.02442.9874020.02898.5
4.88-7.124.1520.01857.3145490.02199.4
7.12-11.393.8660.01663.7916470.01999.2
11.39-49.4514.2960.01572.645470.01796.8

-
Processing

Software
NameVersionClassification
XDSdata reduction
XSCALEdata scaling
PHENIX1.13.2998refinement
PDB_EXTRACT3.24data extraction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.94→49.451 Å / SU ML: 0.25 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 26.2
RfactorNum. reflection% reflection
Rfree0.2125 860 0.82 %
Rwork0.179 --
obs0.1793 104468 98.85 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 115.43 Å2 / Biso mean: 47.1521 Å2 / Biso min: 22.61 Å2
Refinement stepCycle: final / Resolution: 1.94→49.451 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8877 0 120 820 9817
Biso mean--50.1 48.96 -
Num. residues----1130
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 6

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.94-2.06160.34851410.2781170341717598
2.0616-2.22080.25871430.2308172441738799
2.2208-2.44420.27791430.2109172251736899
2.4442-2.79790.21981430.1945173081745199
2.7979-3.52490.22251440.1771172911743599
3.5249-49.46690.16551460.1492175061765299
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°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)
14.44040.31990.9861.23170.06441.318-0.08430.3990.3606-0.08130.03360.0719-0.01270.04350.0330.2647-0.0510.01230.26250.01880.2059-43.8154-55.236312.8568
24.0510.82011.46311.69280.44821.4790.0879-0.42030.21510.158-0.07590.01270.0901-0.233-0.01450.253-0.02820.02650.2456-0.0010.2113-31.5408-54.050628.9507
33.96880.22560.55252.21330.17682.119-0.1030.33421.0587-0.0982-0.0599-0.0436-0.37140.00260.14030.2625-0.0079-0.06570.27920.06320.5238-17.861-38.89223.9335
43.4990.960.87752.6925-0.48061.90390.0083-0.3670.24850.3342-0.00840.0465-0.0555-0.1411-0.01550.2631-0.0028-0.01590.2708-0.01890.2527-22.8134-51.482430.9374
51.24070.87850.13572.85990.58972.7738-0.15410.4677-0.0411-0.88440.4667-0.7943-0.26480.4216-0.31150.4936-0.10050.22230.4794-0.1270.6176-16.9912-83.4702-0.5374
61.3027-0.2569-0.33022.84151.11181.7306-0.16720.2251-0.3137-0.27960.5957-1.5193-0.02320.617-0.36680.3839-0.04930.0950.4727-0.24110.8737-11.462-78.839210.0806
71.17751.03620.70424.80091.71461.25280.0358-0.02460.06910.0253-0.0252-0.108-0.00960.0763-0.00290.27070.03120.0430.3039-0.06320.2893-29.1117-93.60165.9414
81.13730.73190.20483.17870.86172.27880.1410.0458-0.33780.23030.1937-0.73480.34940.4837-0.20750.3440.102-0.0490.3765-0.14730.5286-21.8177-112.2121.0929
91.79920.5021.61413.25660.52891.63220.02920.039-0.117-0.03240.1074-0.30940.11010.1258-0.06560.27150.02460.05580.2895-0.09420.3028-28.9888-102.48721.0197
100.6491-0.317-0.32670.79370.91481.36020.5560.6545-0.9033-0.5232-0.24210.80020.6285-0.0666-0.0690.84280.2409-0.44840.6504-0.35230.8319-73.5819-37.638532.1036
112.5339-0.70670.82272.40780.46491.88370.42870.6469-0.3441-0.3102-0.1989-0.14210.29010.2656-0.19480.38390.1775-0.01220.4213-0.12220.2883-54.8126-26.890243.2953
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid -4 through 116 )A-4 - 116
2X-RAY DIFFRACTION2chain 'A' and (resid 117 through 233 )A117 - 233
3X-RAY DIFFRACTION3chain 'A' and (resid 234 through 322 )A234 - 322
4X-RAY DIFFRACTION4chain 'A' and (resid 323 through 385 )A323 - 385
5X-RAY DIFFRACTION5chain 'B' and (resid -3 through 41 )B-3 - 41
6X-RAY DIFFRACTION6chain 'B' and (resid 42 through 116 )B42 - 116
7X-RAY DIFFRACTION7chain 'B' and (resid 117 through 233 )B117 - 233
8X-RAY DIFFRACTION8chain 'B' and (resid 234 through 309 )B234 - 309
9X-RAY DIFFRACTION9chain 'B' and (resid 317 through 385 )B317 - 385
10X-RAY DIFFRACTION10chain 'C' and (resid -6 through 106 )C-6 - 106
11X-RAY DIFFRACTION11chain 'C' and (resid 107 through 385 )C107 - 385

+
About Yorodumi

-
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

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

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

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
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

Read more