[English] 日本語
Yorodumi
- PDB-2ohn: X-ray crystal structure of beta secretase complexed with 4-(4-flu... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2ohn
TitleX-ray crystal structure of beta secretase complexed with 4-(4-fluorobenzyl)piperidine
ComponentsBeta-secretase 1
KeywordsHYDROLASE / ALTERNATIVE SPLICING / ALZHEIMER'S DISEASE / ASPARTIC PROTEASE / ASPARTYL PROTEASE / BASE / BETA-SECRETASE / GLYCOPROTEIN / MEMAPSIN 2 / TRANSMEMBRANE / ZYMOGEN
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 membrane / endosome / 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
4-(4-FLUOROBENZYL)PIPERIDINE / IODIDE ION / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 Å
AuthorsPatel, S.
CitationJournal: J.Med.Chem. / Year: 2007
Title: Application of fragment screening by X-ray crystallography to beta-Secretase.
Authors: Murray, C.W. / Callaghan, O. / Chessari, G. / Cleasby, A. / Congreve, M. / Frederickson, M. / Hartshorn, M.J. / McMenamin, R. / Patel, S. / Wallis, N.
History
DepositionJan 10, 2007Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 13, 2007Provider: repository / Type: Initial release
Revision 1.1May 1, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Oct 18, 2017Group: Refinement description / Category: software
Revision 1.4Oct 20, 2021Group: Database references / Derived calculations / Category: database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.5Aug 30, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.6Nov 20, 2024Group: Refinement description / Structure summary
Category: pdbx_entry_details / pdbx_modification_feature / software
Item: _software.name
Remark 600 HETEROGEN THERE IS AN EXTRA ATOM H12 IN MOLECULE 4FP. AUTHOR STATES THAT THE MOLECULE 4FP IS ... HETEROGEN THERE IS AN EXTRA ATOM H12 IN MOLECULE 4FP. AUTHOR STATES THAT THE MOLECULE 4FP IS PROTONATED (CHARGED) UNDER THE PH CONDITIONS OF THE EXPERIMENT, AND THIS PROTONATION STATE IS CRITICAL TO THE BINDING MODE OBSERVED.

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Beta-secretase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)45,4946
Polymers44,8411
Non-polymers6525
Water4,252236
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)102.388, 102.388, 170.232
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number178
Space group name H-MP6122
DetailsThe biological assembly is a monomer

-
Components

#1: Protein Beta-secretase 1 / Beta-site APP cleaving enzyme 1 / Beta-site amyloid precursor protein cleaving enzyme 1 / Membrane- ...Beta-site APP cleaving enzyme 1 / Beta-site amyloid precursor protein cleaving enzyme 1 / Membrane-associated aspartic protease 2 / Memapsin-2 / Aspartyl protease 2 / Asp 2 / ASP2


Mass: 44841.395 Da / Num. of mol.: 1 / Fragment: protease domain / Mutation: R56K, R57K
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BACE1, BACE / Plasmid: pET / Species (production host): Escherichia coli / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: P56817, memapsin 2
#2: Chemical ChemComp-IOD / IODIDE ION


Mass: 126.904 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: I
#3: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-4FP / 4-(4-FLUOROBENZYL)PIPERIDINE


Mass: 193.261 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C12H16FN
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 236 / 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: 2.87 Å3/Da / Density % sol: 57.15 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.6
Details: 20-22.5% (w/v) PEG 5000 monomethylether (MME), 200 mM sodium citrate (pH 6.6), 200 mM ammonium iodide, VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-3 / Wavelength: 0.933 Å
DetectorType: ADSC QUANTUM 4 / Detector: CCD / Date: Feb 3, 2003
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.933 Å / Relative weight: 1
ReflectionResolution: 2.15→47.79 Å / Num. all: 29243 / Num. obs: 29243 / % possible obs: 99.6 % / Observed criterion σ(I): 0 / Rmerge(I) obs: 0.085

-
Processing

Software
NameVersionClassificationNB
REFMAC5.2.0019grefinement
PDB_EXTRACT2data extraction
ADSCQUANTUMdata collection
MOSFLMdata reduction
CCP4(SCALA)data scaling
CSearch(IN-HOUSE MR PROGRAMphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 1W50

1w50


Resolution: 2.15→47.79 Å / Cor.coef. Fo:Fc: 0.934 / Cor.coef. Fo:Fc free: 0.896 / SU B: 6.677 / SU ML: 0.173 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.233 / ESU R Free: 0.213 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.285 1487 5.1 %RANDOM
Rwork0.228 ---
all0.231 29243 --
obs0.231 29243 99.44 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 35.333 Å2
Baniso -1Baniso -2Baniso -3
1--0.65 Å2-0.33 Å20 Å2
2---0.65 Å20 Å2
3---0.98 Å2
Refinement stepCycle: LAST / Resolution: 2.15→47.79 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2966 0 38 236 3240
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0223062
X-RAY DIFFRACTIONr_bond_other_d0.0020.022056
X-RAY DIFFRACTIONr_angle_refined_deg1.3881.9444162
X-RAY DIFFRACTIONr_angle_other_deg0.8822.9894985
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.6315375
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.70223.857140
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.27415.031491
X-RAY DIFFRACTIONr_dihedral_angle_4_deg12.8481517
X-RAY DIFFRACTIONr_chiral_restr0.0790.2452
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.023421
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02649
X-RAY DIFFRACTIONr_nbd_refined0.2050.2600
X-RAY DIFFRACTIONr_nbd_other0.2070.22207
X-RAY DIFFRACTIONr_nbtor_refined0.1850.21463
X-RAY DIFFRACTIONr_nbtor_other0.0870.21588
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1790.284
X-RAY DIFFRACTIONr_xyhbond_nbd_other0.0860.22
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.2270.217
X-RAY DIFFRACTIONr_symmetry_vdw_other0.270.264
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.2970.23
X-RAY DIFFRACTIONr_mcbond_it0.05551871
X-RAY DIFFRACTIONr_mcbond_other0.0225767
X-RAY DIFFRACTIONr_mcangle_it0.07663027
X-RAY DIFFRACTIONr_scbond_it0.07161191
X-RAY DIFFRACTIONr_scangle_it0.0887.51135
LS refinement shellResolution: 2.15→2.206 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.372 118 -
Rwork0.282 1985 -
obs-2103 98.78 %

+
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