[English] 日本語
Yorodumi
- PDB-5i3y: Crystal structure of BACE1 in complex with aminoquinoline inhibitor 9 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5i3y
TitleCrystal structure of BACE1 in complex with aminoquinoline inhibitor 9
ComponentsBeta-secretase 1
KeywordsHYDROLASE/HYDROLASE Inhibitor / aspartic protease / amyloid precursor protein / Alzheimer's disease / HYDROLASE-HYDROLASE Inhibitor complex
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 / protein serine/threonine kinase binding / 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 / late endosome / synaptic vesicle / 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 / 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-68K / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsWhittington, D.A. / Long, A.M.
CitationJournal: J.Med.Chem. / Year: 2016
Title: Fragment-Linking Approach Using (19)F NMR Spectroscopy To Obtain Highly Potent and Selective Inhibitors of beta-Secretase.
Authors: Jordan, J.B. / Whittington, D.A. / Bartberger, M.D. / Sickmier, E.A. / Chen, K. / Cheng, Y. / Judd, T.
History
DepositionFeb 11, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 30, 2016Provider: repository / Type: Initial release
Revision 1.1Apr 20, 2016Group: Database references
Revision 1.2May 11, 2016Group: Database references
Revision 1.3Nov 1, 2017Group: Author supporting evidence / Database references / Derived calculations
Category: citation / pdbx_struct_assembly_auth_evidence / pdbx_struct_oper_list
Item: _citation.journal_id_CSD / _pdbx_struct_oper_list.symmetry_operation
Revision 1.4Sep 27, 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)46,4402
Polymers45,8221
Non-polymers6181
Water3,981221
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)102.788, 102.788, 170.300
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-684-

HOH

DetailsMonomer by size exclusion chromatography

-
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: R56K, R57K
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-68K / N-(6-{2-[2-(2-amino-3-{3-[(3,3-dimethylbutyl)amino]-3-oxopropyl}quinolin-6-yl)phenyl]ethyl}pyridin-3-yl)-4-fluorobenzamide


Mass: 617.755 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C38H40FN5O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 221 / 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: 2.83 Å3/Da / Density % sol: 56.6 %
Crystal growTemperature: 298 K / Method: vapor diffusion / pH: 5.5
Details: 1.5 M ammonium sulfate, 0.2 M lithium chloride, 0.1 M bis-tris (pH 5.5)
PH range: 5.5-6.0

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-BM / Wavelength: 1 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Jul 11, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.15→50 Å / Num. obs: 29605 / % possible obs: 99.8 % / Observed criterion σ(I): -3 / Redundancy: 10.8 % / Biso Wilson estimate: 26.2 Å2 / Rmerge(I) obs: 0.135 / Net I/av σ(I): 15.3 / Net I/σ(I): 14.3
Reflection shell
Resolution (Å)Redundancy (%)Mean I/σ(I) obsDiffraction-ID% possible allRmerge(I) obs
2.15-2.2310.92.151100
2.23-2.3210.911000.887
2.32-2.4210.911000.715
2.42-2.5510.911000.555
2.55-2.7110.811000.418
2.71-2.9210.911000.286
2.92-3.2110.811000.184
3.21-3.6810.811000.106
3.68-4.6310.7199.70.062
4.63-5010.1198.70.04

-
Processing

Software
NameVersionClassification
HKL-2000data scaling
REFMACrefinement
PDB_EXTRACT3.2data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1W50

1w50


Resolution: 2.15→50 Å / Cor.coef. Fo:Fc: 0.942 / Cor.coef. Fo:Fc free: 0.919 / SU B: 8.99 / SU ML: 0.13 / SU R Cruickshank DPI: 0.2001 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.2 / ESU R Free: 0.176
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES: WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2377 1462 5 %RANDOM
Rwork0.1995 ---
obs0.2014 27922 99.19 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 225.41 Å2 / Biso mean: 40.743 Å2 / Biso min: 8.95 Å2
Baniso -1Baniso -2Baniso -3
1--0.05 Å2-0.03 Å20 Å2
2---0.05 Å20 Å2
3---0.08 Å2
Refinement stepCycle: final / Resolution: 2.15→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2913 0 46 221 3180
Biso mean--19.75 32.51 -
Num. residues----369
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.023039
X-RAY DIFFRACTIONr_bond_other_d0.0010.022040
X-RAY DIFFRACTIONr_angle_refined_deg1.2521.9634131
X-RAY DIFFRACTIONr_angle_other_deg0.8233.0054903
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.785365
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.29623.723137
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.7915478
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.5441517
X-RAY DIFFRACTIONr_chiral_restr0.070.2444
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0213374
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02644
LS refinement shellResolution: 2.151→2.207 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.311 92 -
Rwork0.26 1797 -
all-1889 -
obs--92.28 %
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)
16.963-0.5023-2.46892.48510.63513.3227-0.44150.3361-0.73030.0431-0.01740.12320.4107-0.17160.45890.091-0.02780.08620.056-0.05420.109519.30228.304-6.6395
28.8316-3.7484-3.38473.9481.06363.71690.48990.51131.1931-0.1946-0.1321-0.5384-0.3478-0.2637-0.35790.07430.01260.07850.09180.05680.17516.270447.45171.9794
38.234-4.2866-3.89475.05770.54213.74450.7817-0.52613.4868-0.33120.1977-2.8866-0.64110.671-0.97940.209-0.05850.29510.2274-0.14481.895315.346757.86395.7073
49.5006-5.5938-3.32895.03231.00341.77940.1496-0.02471.0644-0.09210.1265-0.7639-0.1381-0.0075-0.27610.1336-0.02680.02340.05850.00340.14885.505247.21635.9807
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A-1 - 145
2X-RAY DIFFRACTION2A146 - 251
3X-RAY DIFFRACTION3A252 - 321
4X-RAY DIFFRACTION4A322 - 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://pdbjlvh1.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