[English] 日本語
Yorodumi
- PDB-6eqm: Crystal Structure of Human BACE-1 in Complex with CNP520 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6eqm
TitleCrystal Structure of Human BACE-1 in Complex with CNP520
ComponentsBeta-secretase 1
KeywordsHYDROLASE / Structure-based drug design / Alzheimer's disease / aspartic acid proteinase
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 ...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 / detection of mechanical stimulus involved in sensory perception of pain / cellular response to copper ion / presynaptic modulation of chemical synaptic transmission / hippocampal mossy fiber to CA3 synapse / multivesicular body / response to lead ion / trans-Golgi network / recycling endosome / protein processing / cellular response to amyloid-beta / positive regulation of neuron apoptotic process / synaptic vesicle / late endosome / peptidase activity / amyloid-beta binding / endopeptidase activity / amyloid fibril formation / aspartic-type endopeptidase activity / lysosome / early endosome / endosome membrane / endosome / membrane raft / Amyloid fiber formation / axon / endoplasmic reticulum lumen / neuronal cell body / dendrite / Golgi apparatus / enzyme binding / cell surface / 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-BUH / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.35 Å
AuthorsRondeau, J.-M. / Wirth, E.
CitationJournal: EMBO Mol Med / Year: 2018
Title: The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease.
Authors: Neumann, U. / Ufer, M. / Jacobson, L.H. / Rouzade-Dominguez, M.L. / Huledal, G. / Kolly, C. / Luond, R.M. / Machauer, R. / Veenstra, S.J. / Hurth, K. / Rueeger, H. / Tintelnot-Blomley, M. / ...Authors: Neumann, U. / Ufer, M. / Jacobson, L.H. / Rouzade-Dominguez, M.L. / Huledal, G. / Kolly, C. / Luond, R.M. / Machauer, R. / Veenstra, S.J. / Hurth, K. / Rueeger, H. / Tintelnot-Blomley, M. / Staufenbiel, M. / Shimshek, D.R. / Perrot, L. / Frieauff, W. / Dubost, V. / Schiller, H. / Vogg, B. / Beltz, K. / Avrameas, A. / Kretz, S. / Pezous, N. / Rondeau, J.M. / Beckmann, N. / Hartmann, A. / Vormfelde, S. / David, O.J. / Galli, B. / Ramos, R. / Graf, A. / Lopez Lopez, C.
History
DepositionOct 13, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 19, 2018Provider: repository / Type: Initial release
Revision 1.1Sep 26, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_abbrev / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Nov 21, 2018Group: Data collection / Database references / Category: citation / citation_author / pdbx_database_proc
Item: _citation.journal_volume / _citation_author.identifier_ORCID
Revision 1.3May 1, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)45,2912
Polymers44,7771
Non-polymers5141
Water5,711317
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area16770 Å2
MethodPISA
Unit cell
Length a, b, c (Å)47.660, 76.650, 104.540
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
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: 44777.336 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BACE1, BACE, KIAA1149 / Plasmid: pET24 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P56817, memapsin 2
#2: Chemical ChemComp-BUH / ~{N}-[6-[(3~{R},6~{R})-5-azanyl-3,6-dimethyl-6-(trifluoromethyl)-2~{H}-1,4-oxazin-3-yl]-5-fluoranyl-pyridin-2-yl]-3-chloranyl-5-(trifluoromethyl)pyridine-2-carboxamide


Mass: 513.797 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H15ClF7N5O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 317 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.13 Å3/Da / Density % sol: 42.31 % / Description: Rod
Crystal growTemperature: 292 K / Method: vapor diffusion, hanging drop / pH: 5.5 / Details: 15% PEG 1,500 in water

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.99997 Å
DetectorType: PSI PILATUS 6M / Detector: PIXEL / Date: Mar 2, 2013 / Details: mirrors
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99997 Å / Relative weight: 1
ReflectionResolution: 1.35→19.77 Å / Num. obs: 83784 / % possible obs: 98.8 % / Observed criterion σ(I): -3 / Redundancy: 6.509 % / Biso Wilson estimate: 19.31 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.052 / Rrim(I) all: 0.056 / Χ2: 1.026 / Net I/σ(I): 16.7
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsCC1/2Rrim(I) all% possible all
1.35-1.396.5491.1531.6860370.6841.25197.6
1.39-1.426.2540.972259180.7261.05997.6
1.42-1.466.4050.7472.5757230.8350.81298.1
1.46-1.516.7790.5323.6856470.9170.57698.2
1.51-1.566.6930.3974.8854550.9530.4398.4
1.56-1.616.540.335.8452770.9630.35898.7
1.61-1.676.2130.2437.3851150.9770.26598.5
1.67-1.746.5790.17710.0449500.9860.19298.7
1.74-1.826.8280.13313.3947440.9920.14399
1.82-1.916.7390.09517.7345720.9950.10399.3
1.91-2.016.6030.07322.4843430.9970.07999.4
2.01-2.136.1120.05926.2141200.9970.06599.3
2.13-2.286.760.05131.4138940.9980.05699.6
2.28-2.466.780.04734.536460.9980.0599.8
2.46-2.76.5880.04336.9533480.9980.04799.7
2.7-3.025.9740.03938.0730780.9980.04399.5
3.02-3.496.4120.03643.4727140.9990.03999.5
3.49-4.276.5020.03346.6223170.9990.03699.7
4.27-6.045.9070.03145.1218210.9990.03499.3
6.04-19.776.3370.02946.5810650.9990.03299.3

-
Processing

Software
NameVersionClassification
XSCALEJuly 4, 2012data scaling
BUSTER2.11.4refinement
PDB_EXTRACT3.22data extraction
XDSSept. 26, 2012data reduction
BUSTER2.11.4phasing
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: in house structure

Resolution: 1.35→19.77 Å / Cor.coef. Fo:Fc: 0.9633 / Cor.coef. Fo:Fc free: 0.9559 / SU R Cruickshank DPI: 0.054 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.056 / SU Rfree Blow DPI: 0.056 / SU Rfree Cruickshank DPI: 0.054
RfactorNum. reflection% reflectionSelection details
Rfree0.2001 4188 5 %RANDOM
Rwork0.1836 ---
obs0.1844 83746 98.79 %-
Displacement parametersBiso max: 106.53 Å2 / Biso mean: 24.78 Å2 / Biso min: 11.62 Å2
Baniso -1Baniso -2Baniso -3
1--3.5098 Å20 Å20 Å2
2--0.3305 Å20 Å2
3---3.1793 Å2
Refine analyzeLuzzati coordinate error obs: 0.162 Å
Refinement stepCycle: final / Resolution: 1.35→19.77 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2974 0 34 317 3325
Biso mean--19.54 34.16 -
Num. residues----378
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1056SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes72HARMONIC2
X-RAY DIFFRACTIONt_gen_planes467HARMONIC5
X-RAY DIFFRACTIONt_it3156HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion404SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact3822SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d3156HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg4315HARMONIC21.09
X-RAY DIFFRACTIONt_omega_torsion4.74
X-RAY DIFFRACTIONt_other_torsion15.3
LS refinement shellResolution: 1.35→1.39 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.2292 302 5.01 %
Rwork0.2296 5724 -
all0.2296 6026 -
obs--98.79 %

+
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