[English] 日本語
Yorodumi
- PDB-2g47: Crystal structure of human insulin-degrading enzyme in complex wi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2g47
TitleCrystal structure of human insulin-degrading enzyme in complex with amyloid-beta (1-40)
Components
  • Insulin-degrading enzyme
  • amyloid protein beta A4
KeywordsHYDROLASE / protein-peptide complex
Function / homology
Function and homology information


insulysin / ubiquitin recycling / insulin catabolic process / insulin metabolic process / amyloid-beta clearance by cellular catabolic process / hormone catabolic process / bradykinin catabolic process / regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury ...insulysin / ubiquitin recycling / insulin catabolic process / insulin metabolic process / amyloid-beta clearance by cellular catabolic process / hormone catabolic process / bradykinin catabolic process / regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity / smooth endoplasmic reticulum calcium ion homeostasis / axon midline choice point recognition / astrocyte activation involved in immune response / regulation of spontaneous synaptic transmission / mating behavior / NMDA selective glutamate receptor signaling pathway / ubiquitin-modified protein reader activity / ciliary rootlet / Lysosome Vesicle Biogenesis / insulin binding / PTB domain binding / Golgi-associated vesicle / positive regulation of amyloid fibril formation / neuron remodeling / regulation of aerobic respiration / : / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / peptide catabolic process / suckling behavior / nuclear envelope lumen / dendrite development / amyloid-beta clearance / COPII-coated ER to Golgi transport vesicle / presynaptic active zone / modulation of excitatory postsynaptic potential / TRAF6 mediated NF-kB activation / peroxisomal matrix / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / The NLRP3 inflammasome / regulation of presynapse assembly / transition metal ion binding / negative regulation of long-term synaptic potentiation / regulation of multicellular organism growth / intracellular copper ion homeostasis / negative regulation of neuron differentiation / ECM proteoglycans / smooth endoplasmic reticulum / positive regulation of T cell migration / spindle midzone / amyloid-beta metabolic process / Purinergic signaling in leishmaniasis infection / positive regulation of calcium-mediated signaling / protein serine/threonine kinase binding / positive regulation of chemokine production / clathrin-coated pit / regulation of peptidyl-tyrosine phosphorylation / forebrain development / Notch signaling pathway / Insulin receptor recycling / Mitochondrial protein degradation / neuron projection maintenance / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / ionotropic glutamate receptor signaling pathway / positive regulation of glycolytic process / cholesterol metabolic process / positive regulation of mitotic cell cycle / response to interleukin-1 / adult locomotory behavior / extracellular matrix organization / axonogenesis / platelet alpha granule lumen / trans-Golgi network membrane / positive regulation of peptidyl-threonine phosphorylation / proteolysis involved in protein catabolic process / dendritic shaft / learning / positive regulation of interleukin-1 beta production / positive regulation of long-term synaptic potentiation / locomotory behavior / central nervous system development / endosome lumen / astrocyte activation / Peroxisomal protein import / positive regulation of JNK cascade / Post-translational protein phosphorylation / peptide binding / synapse organization / regulation of long-term neuronal synaptic plasticity / microglial cell activation / TAK1-dependent IKK and NF-kappa-B activation
Similarity search - Function
Peptidase M16, middle/third domain / Middle or third domain of peptidase_M16 / Cytochrome Bc1 Complex; Chain A, domain 1 / Metalloenzyme, LuxS/M16 peptidase-like / Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, copper-binding domain conserved site / Amyloidogenic glycoprotein, copper-binding domain superfamily / Copper-binding of amyloid precursor, CuBD / Amyloid precursor protein (APP) copper-binding (CuBD) domain signature. / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily ...Peptidase M16, middle/third domain / Middle or third domain of peptidase_M16 / Cytochrome Bc1 Complex; Chain A, domain 1 / Metalloenzyme, LuxS/M16 peptidase-like / Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, copper-binding domain conserved site / Amyloidogenic glycoprotein, copper-binding domain superfamily / Copper-binding of amyloid precursor, CuBD / Amyloid precursor protein (APP) copper-binding (CuBD) domain signature. / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Beta-amyloid peptide (beta-APP) / Amyloidogenic glycoprotein, amyloid-beta peptide / Beta-amyloid precursor protein C-terminal / Amyloidogenic glycoprotein, intracellular domain, conserved site / Beta-amyloid precursor protein C-terminus / Amyloid precursor protein (APP) intracellular domain signature. / Amyloid precursor protein (APP) E1 domain profile. / Amyloid precursor protein (APP) E2 domain profile. / Amyloidogenic glycoprotein, extracellular / Amyloidogenic glycoprotein, heparin-binding / Amyloidogenic glycoprotein, E2 domain / E2 domain superfamily / Amyloidogenic glycoprotein, heparin-binding domain superfamily / Amyloid A4 N-terminal heparin-binding / E2 domain of amyloid precursor protein / amyloid A4 / Amyloidogenic glycoprotein / Peptidase M16, zinc-binding site / Insulinase family, zinc-binding region signature. / Peptidase M16, C-terminal / Peptidase M16 inactive domain / Peptidase M16, N-terminal / Insulinase (Peptidase family M16) / Metalloenzyme, LuxS/M16 peptidase-like / Proteinase inhibitor I2, Kunitz, conserved site / Pancreatic trypsin inhibitor (Kunitz) family signature. / BPTI/Kunitz family of serine protease inhibitors. / Pancreatic trypsin inhibitor Kunitz domain / Kunitz/Bovine pancreatic trypsin inhibitor domain / Pancreatic trypsin inhibitor (Kunitz) family profile. / Pancreatic trypsin inhibitor Kunitz domain superfamily / PH-like domain superfamily / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
1,4-DIETHYLENE DIOXIDE / Amyloid-beta precursor protein / Insulin-degrading enzyme
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsShen, Y. / Tang, W.-J.
CitationJournal: Nature / Year: 2006
Title: Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism.
Authors: Shen, Y. / Joachimiak, A. / Rosner, M.R. / Tang, W.J.
History
DepositionFeb 21, 2006Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 24, 2006Provider: repository / Type: Initial release
Revision 1.1May 1, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Oct 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 1.4Feb 14, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Insulin-degrading enzyme
B: Insulin-degrading enzyme
C: amyloid protein beta A4
D: amyloid protein beta A4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)238,2786
Polymers238,1024
Non-polymers1762
Water19,2041066
1
A: Insulin-degrading enzyme
C: amyloid protein beta A4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)119,1393
Polymers119,0512
Non-polymers881
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2180 Å2
ΔGint-7 kcal/mol
Surface area38050 Å2
MethodPISA
2
B: Insulin-degrading enzyme
D: amyloid protein beta A4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)119,1393
Polymers119,0512
Non-polymers881
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2210 Å2
ΔGint-5 kcal/mol
Surface area38190 Å2
MethodPISA
Unit cell
Length a, b, c (Å)262.433, 262.433, 90.706
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number170
Space group name H-MP65
DetailsThe biological assembly is a monomer.

-
Components

#1: Protein Insulin-degrading enzyme / Insulysin / Insulinase / Insulin protease


Mass: 114715.141 Da / Num. of mol.: 2 / Mutation: E111Q
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IDE / Plasmid: pProEx / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta(DE3) / References: UniProt: P14735, insulysin
#2: Protein/peptide amyloid protein beta A4


Mass: 4335.852 Da / Num. of mol.: 2 / Source method: obtained synthetically
Details: This sequence occurs naturally in Homo sapiens (Humans)
References: UniProt: P05067*PLUS
#3: Chemical ChemComp-DIO / 1,4-DIETHYLENE DIOXIDE


Mass: 88.105 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C4H8O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1066 / 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: 3.78 Å3/Da / Density % sol: 67.49 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 10% PEGMME 5000, 0.1M HEPES, 10% diaoxane, 5% tacsimate, pH 7.0, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.9 Å
DetectorType: ADSC QUANTUM 4 / Detector: CCD / Date: Aug 23, 2005
RadiationMonochromator: graphite / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9 Å / Relative weight: 1
ReflectionResolution: 2.1→30 Å / Num. all: 194459 / Num. obs: 194459 / % possible obs: 99 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Redundancy: 7.6 % / Biso Wilson estimate: 19.2 Å2 / Rsym value: 0.076 / Net I/σ(I): 24.2
Reflection shellResolution: 2.1→2.18 Å / Redundancy: 4.4 % / Rmerge(I) obs: 0.55 / Mean I/σ(I) obs: 2.3 / % possible all: 77

-
Processing

Software
NameVersionClassification
CNS1.1refinement
HKL-2000data reduction
SCALEPACKdata scaling
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.1→29.77 Å / Rfactor Rfree error: 0.002 / Data cutoff high absF: 114223.13 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.223 18633 10 %RANDOM
Rwork0.203 ---
obs0.203 187264 90.5 %-
Solvent computationSolvent model: FLAT MODEL / Bsol: 52.4308 Å2 / ksol: 0.37074 e/Å3
Displacement parametersBiso mean: 34.6 Å2
Baniso -1Baniso -2Baniso -3
1--3.06 Å21.21 Å20 Å2
2---3.06 Å20 Å2
3---6.12 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.27 Å0.24 Å
Luzzati d res low-5 Å
Luzzati sigma a0.25 Å0.22 Å
Refinement stepCycle: LAST / Resolution: 2.1→29.77 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms15884 0 12 1066 16962
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_bond_d0.008
X-RAY DIFFRACTIONc_bond_d_na
X-RAY DIFFRACTIONc_bond_d_prot
X-RAY DIFFRACTIONc_angle_d
X-RAY DIFFRACTIONc_angle_d_na
X-RAY DIFFRACTIONc_angle_d_prot
X-RAY DIFFRACTIONc_angle_deg1.3
X-RAY DIFFRACTIONc_angle_deg_na
X-RAY DIFFRACTIONc_angle_deg_prot
X-RAY DIFFRACTIONc_dihedral_angle_d23.1
X-RAY DIFFRACTIONc_dihedral_angle_d_na
X-RAY DIFFRACTIONc_dihedral_angle_d_prot
X-RAY DIFFRACTIONc_improper_angle_d0.81
X-RAY DIFFRACTIONc_improper_angle_d_na
X-RAY DIFFRACTIONc_improper_angle_d_prot
X-RAY DIFFRACTIONc_mcbond_it1.291.5
X-RAY DIFFRACTIONc_mcangle_it1.92
X-RAY DIFFRACTIONc_scbond_it2.312
X-RAY DIFFRACTIONc_scangle_it3.462.5
LS refinement shellResolution: 2.1→2.23 Å / Rfactor Rfree error: 0.006 / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.277 2333 9.9 %
Rwork0.26 21339 -
obs--69 %
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1protein_rep.paramprotein.top
X-RAY DIFFRACTION2water_rep.paramwater.top
X-RAY DIFFRACTION3dox.pardox.top

+
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