[English] 日本語
Yorodumi
- PDB-5uyu: Crystal structure of BACE1 in complex with 2-aminooxazoline-3-aza... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5uyu
TitleCrystal structure of BACE1 in complex with 2-aminooxazoline-3-azaxanthene compound 12
ComponentsBeta-secretase 1
KeywordsHYDROLASE / aspartic protease / Alzheimers disease / APP / amyloid precursor protein
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 / lysosome / aspartic-type endopeptidase activity / early endosome / endosome membrane / endosome / membrane raft / Amyloid fiber formation / endoplasmic reticulum lumen / axon / 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-8QV / IODIDE ION / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsWhittington, D.A. / Long, A.M. / Sickmier, E.A.
CitationJournal: Medchemcomm / Year: 2017
Title: Development of 2-aminooxazoline 3-azaxanthene beta-amyloid cleaving enzyme (BACE) inhibitors with improved selectivity against Cathepsin D.
Authors: Low, J.D. / Bartberger, M.D. / Chen, K. / Cheng, Y. / Fielden, M.R. / Gore, V. / Hickman, D. / Liu, Q. / Allen Sickmier, E. / Vargas, H.M. / Werner, J. / White, R.D. / Whittington, D.A. / ...Authors: Low, J.D. / Bartberger, M.D. / Chen, K. / Cheng, Y. / Fielden, M.R. / Gore, V. / Hickman, D. / Liu, Q. / Allen Sickmier, E. / Vargas, H.M. / Werner, J. / White, R.D. / Whittington, D.A. / Wood, S. / Minatti, A.E.
History
DepositionFeb 24, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 17, 2017Provider: repository / Type: Initial release
Revision 1.1Nov 22, 2017Group: Refinement description / Category: software
Revision 1.2Aug 29, 2018Group: Data collection / Database references / Derived calculations
Category: citation / citation_author / pdbx_struct_special_symmetry
Item: _citation.journal_id_ISSN / _citation.journal_volume ..._citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.3Oct 4, 2023Group: 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)47,0008
Polymers45,8221
Non-polymers1,1777
Water6,666370
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)102.287, 102.287, 170.374
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number178
Space group name H-MP6122
Components on special symmetry positions
IDModelComponents
11A-738-

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: 45822.445 Da / Num. of mol.: 1 / Fragment: UNP residues 43-453 / Mutation: R5K, R4K
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-IOD / IODIDE ION / Iodide


Mass: 126.904 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: I
#3: Chemical ChemComp-8QV / (5S)-3-(3,6-dihydro-2H-pyran-4-yl)-7-[5-(prop-1-yn-1-yl)pyridin-3-yl]-5'H-spiro[1-benzopyrano[2,3-c]pyridine-5,4'-[1,3]oxazol]-2'-amine


Mass: 450.489 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C27H22N4O3
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 370 / 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: 2.81 Å3/Da / Density % sol: 56.19 %
Crystal growTemperature: 298 K / Method: vapor diffusion / pH: 6.6
Details: 21% polyethylene glycol 5000 MME, 180 mM sodium citrate (pH 6.6), 200 mM ammonium iodide, 3% (v/v) DMSO

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.5418 Å
DetectorType: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Feb 19, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.9→50 Å / Num. obs: 41991 / % possible obs: 99.4 % / Observed criterion σ(I): -3 / Redundancy: 6.8 % / Rmerge(I) obs: 0.071 / Χ2: 1.027 / Net I/av σ(I): 17.2 / Net I/σ(I): 15.3
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique allΧ2% possible all
1.9-1.9730.4532.439351.00195
1.97-2.054.30.3390.94799.3
2.05-2.146.70.2741.002100
2.14-2.257.70.2080.992100
2.25-2.397.80.1570.987100
2.39-2.587.80.1220.957100
2.58-2.847.80.090.921100
2.84-3.257.90.0650.859100
3.25-4.097.80.0530.802100
4.09-507.40.051.73299.7

-
Processing

Software
NameVersionClassification
HKL-2000data scaling
REFMACrefinement
PDB_EXTRACT3.22data extraction
HKL-2000data reduction
AMoREphasing
DENZOdata reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1W50

1w50


Resolution: 1.9→50 Å / Cor.coef. Fo:Fc: 0.945 / Cor.coef. Fo:Fc free: 0.941 / SU B: 5.922 / SU ML: 0.101 / SU R Cruickshank DPI: 0.1409 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.141 / ESU R Free: 0.128
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES: WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.228 2116 5 %RANDOM
Rwork0.2052 ---
obs0.2064 39815 99.42 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 112.35 Å2 / Biso mean: 29.7 Å2 / Biso min: 13.72 Å2
Baniso -1Baniso -2Baniso -3
1--0.25 Å2-0.13 Å20 Å2
2---0.25 Å20 Å2
3---0.38 Å2
Refinement stepCycle: final / Resolution: 1.9→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2914 0 45 370 3329
Biso mean--28.91 36.12 -
Num. residues----370
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.023035
X-RAY DIFFRACTIONr_bond_other_d0.0010.022037
X-RAY DIFFRACTIONr_angle_refined_deg1.2581.9614127
X-RAY DIFFRACTIONr_angle_other_deg0.8353.0044908
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.3675367
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.70523.723137
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.21415476
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.1981517
X-RAY DIFFRACTIONr_chiral_restr0.0680.2444
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0213379
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02647
LS refinement shellResolution: 1.9→1.949 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.41 129 -
Rwork0.392 2527 -
all-2656 -
obs--93.52 %
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)
13.62230.97351.18722.18040.67091.5943-0.2073-0.09140.1687-0.13150.01790.1335-0.1770.00060.18940.09140.0327-0.05360.0245-0.01620.038571.491161.06145.3411
24.12291.88861.10072.57150.17982.18150.0717-0.1324-0.4760.10030.0192-0.28010.0633-0.1112-0.09090.08450.0123-0.04710.01230.00530.07557.960143.073-2.3633
32.55450.73181.16692.9093-0.33882.15770.22130.034-0.91460.22950.0503-1.18080.33360.3371-0.27160.17120.0101-0.16440.1135-0.03650.646766.738929.5102-3.0756
43.31082.13871.70663.60440.06441.4504-0.02930.1125-0.40680.00680.1378-0.46510.0091-0.061-0.10850.072-0.0266-0.01820.0955-0.03290.078657.075542.1809-7.3779
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A-1 - 147
2X-RAY DIFFRACTION2A148 - 239
3X-RAY DIFFRACTION3A240 - 328
4X-RAY DIFFRACTION4A329 - 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