[English] 日本語
Yorodumi
- PDB-4trz: Structure of BACE1 complex with 2-thiophenyl HEA-type inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4trz
TitleStructure of BACE1 complex with 2-thiophenyl HEA-type inhibitor
Components
  • 2-thiophenyl HEA-type inhibitor
  • Beta-secretase 1
KeywordsHydrolase/Hydrolase inhibitor / hydrase proteinase converting / designed inhibitor / hydrase-inhibitor complex / 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 / detection of mechanical stimulus involved in sensory perception of pain / amyloid-beta metabolic process / cellular response to manganese ion ...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 / detection of mechanical stimulus involved in sensory perception of pain / amyloid-beta metabolic process / cellular response to manganese ion / prepulse inhibition / protein serine/threonine kinase binding / cellular response to copper ion / presynaptic modulation of chemical synaptic transmission / multivesicular body / hippocampal mossy fiber to CA3 synapse / response to lead ion / trans-Golgi network / recycling endosome / protein processing / positive regulation of neuron apoptotic process / cellular response to amyloid-beta / late endosome / synaptic vesicle / 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
2-thiophenyl HEA-type inhibitor / Beta-secretase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 3.25 Å
Model detailssyn-HEA, aki092
AuthorsAkaji, K. / Teruya, K. / Akiyama, T. / Sanjho, A. / Yamashita, E. / Nakagawa, A.
CitationJournal: Bioorg.Med.Chem. / Year: 2015
Title: Evaluation of transition-state mimics in a superior BACE1 cleavage sequence as peptide-mimetic BACE1 inhibitors
Authors: Hattori, Y. / Kobayashi, K. / Deguchi, A. / Nohara, Y. / Akiyama, T. / Teruya, K. / Sanjoh, A. / Nakagawa, A. / Yamashita, E. / Akaji, K.
History
DepositionJun 18, 2014Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Jul 1, 2015Provider: repository / Type: Initial release
Revision 1.1Sep 2, 2015Group: Database references
Revision 1.2Sep 9, 2015Group: Database references
Revision 1.3Jan 29, 2020Group: Data collection / Database references / Derived calculations
Category: citation / diffrn_source / pdbx_struct_oper_list
Item: _citation.journal_id_CSD / _diffrn_source.pdbx_synchrotron_site / _pdbx_struct_oper_list.symmetry_operation
Revision 1.4Nov 8, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / diffrn_radiation_wavelength / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 2.0Nov 15, 2023Group: Atomic model / Data collection / Derived calculations
Category: atom_site / chem_comp_atom ...atom_site / chem_comp_atom / chem_comp_bond / pdbx_validate_main_chain_plane / pdbx_validate_rmsd_angle / pdbx_validate_rmsd_bond / struct_conn
Item: _atom_site.auth_atom_id / _atom_site.label_atom_id ..._atom_site.auth_atom_id / _atom_site.label_atom_id / _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_1 / _chem_comp_bond.atom_id_2 / _struct_conn.ptnr2_label_atom_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Beta-secretase 1
B: Beta-secretase 1
C: Beta-secretase 1
D: 2-thiophenyl HEA-type inhibitor
E: 2-thiophenyl HEA-type inhibitor
F: 2-thiophenyl HEA-type inhibitor


Theoretical massNumber of molelcules
Total (without water)131,8916
Polymers131,8916
Non-polymers00
Water19811
1
A: Beta-secretase 1
D: 2-thiophenyl HEA-type inhibitor


Theoretical massNumber of molelcules
Total (without water)43,9642
Polymers43,9642
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1300 Å2
ΔGint-6 kcal/mol
Surface area16490 Å2
MethodPISA
2
B: Beta-secretase 1
E: 2-thiophenyl HEA-type inhibitor


Theoretical massNumber of molelcules
Total (without water)43,9642
Polymers43,9642
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1260 Å2
ΔGint-5 kcal/mol
Surface area16680 Å2
MethodPISA
3
C: Beta-secretase 1
F: 2-thiophenyl HEA-type inhibitor


Theoretical massNumber of molelcules
Total (without water)43,9642
Polymers43,9642
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1310 Å2
ΔGint-6 kcal/mol
Surface area16730 Å2
MethodPISA
Unit cell
Length a, b, c (Å)81.872, 102.420, 101.587
Angle α, β, γ (deg.)90.000, 103.490, 90.000
Int Tables number4
Space group name H-MP1211
Detailsbiological unit is the same as asym.

-
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: 43281.832 Da / Num. of mol.: 3 / Fragment: UNP residues 60-447
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BACE1, BACE, KIAA1149 / Plasmid: pET11a / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P56817, memapsin 2
#2: Protein/peptide 2-thiophenyl HEA-type inhibitor


Type: Peptide-like / Class: Enzyme inhibitor / Mass: 681.863 Da / Num. of mol.: 3 / Source method: obtained synthetically / Details: designed and chemically synthesized / Source: (synth.) synthetic construct (others) / References: 2-thiophenyl HEA-type inhibitor
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 11 / 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: 3.19 Å3/Da / Density % sol: 61.44 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 5
Details: 100mM Sodium citrate, 200mM Ammonium sulfate, 23%(v/v) PEG 10000

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SPring-8 / Beamline: BL44XU / Wavelength: 0.9 Å
DetectorType: RAYONIX MX300HE / Detector: CCD / Date: Dec 4, 2013 / Details: horizontal focusing mirror
RadiationMonochromator: double-crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9 Å / Relative weight: 1
ReflectionResolution: 3.16→50 Å / Num. obs: 27835 / % possible obs: 100 % / Redundancy: 3.8 % / Net I/σ(I): 16
Reflection shellResolution: 3.16→3.24 Å / Redundancy: 3.8 % / % possible all: 100

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
DENZOdata collection
SCALEPACKdata reduction
MOLREPmodel building
REFMAC5.8.0049refinement
PDB_EXTRACT3.14data extraction
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2QP8

2qp8


Resolution: 3.25→49.1 Å / Cor.coef. Fo:Fc: 0.88 / Cor.coef. Fo:Fc free: 0.862 / SU ML: 0 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.537 / ESU R Free: 0.603 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2951 1315 5.1 %RANDOM
Rwork0.2631 24467 --
obs0.2647 25782 99.22 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 275.33 Å2 / Biso min: 20 Å2
Baniso -1Baniso -2Baniso -3
1-0.09 Å2-0 Å20.24 Å2
2---0.49 Å20 Å2
3---0.25 Å2
Refinement stepCycle: final / Resolution: 3.25→49.1 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9288 0 79 11 9378
Biso mean--20 52.95 -
Num. residues----1171
LS refinement shellResolution: 3.246→3.33 Å
RfactorNum. reflection% reflection
Rfree0.402 90 -
Rwork-1652 -
obs--91.35 %

+
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