[English] 日本語
Yorodumi
- PDB-3e4z: Crystal structure of human insulin degrading enzyme in complex wi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3e4z
TitleCrystal structure of human insulin degrading enzyme in complex with insulin-like growth factor II
Components
  • Insulin-degrading enzyme
  • Insulin-like growth factor II
KeywordsHYDROLASE/HORMONE / IDE / IGF-II / DEGRADING / COMPLEX / Alternative splicing / Glycoprotein / Growth factor / Mitogen / Polymorphism / Secreted / HYDROLASE-HORMONE COMPLEX
Function / homology
Function and homology information


spongiotrophoblast cell proliferation / positive regulation of skeletal muscle tissue growth / negative regulation of muscle cell differentiation / embryonic placenta morphogenesis / insulysin / regulation of muscle cell differentiation / ubiquitin recycling / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / insulin catabolic process / insulin metabolic process ...spongiotrophoblast cell proliferation / positive regulation of skeletal muscle tissue growth / negative regulation of muscle cell differentiation / embryonic placenta morphogenesis / insulysin / regulation of muscle cell differentiation / ubiquitin recycling / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / insulin catabolic process / insulin metabolic process / IRS-related events triggered by IGF1R / genomic imprinting / positive regulation of organ growth / amyloid-beta clearance by cellular catabolic process / hormone catabolic process / bradykinin catabolic process / exocrine pancreas development / positive regulation of multicellular organism growth / ubiquitin-modified protein reader activity / positive regulation of vascular endothelial cell proliferation / insulin binding / regulation of aerobic respiration / peptide catabolic process / transmembrane receptor protein tyrosine kinase activator activity / positive regulation of activated T cell proliferation / amyloid-beta clearance / peroxisomal matrix / positive regulation of cell division / positive regulation of glycogen biosynthetic process / embryonic placenta development / SHC-related events triggered by IGF1R / amyloid-beta metabolic process / positive regulation of insulin receptor signaling pathway / striated muscle cell differentiation / Insulin receptor recycling / protein serine/threonine kinase activator activity / positive regulation of mitotic nuclear division / insulin-like growth factor receptor signaling pathway / platelet alpha granule lumen / proteolysis involved in protein catabolic process / Peroxisomal protein import / animal organ morphogenesis / peptide binding / insulin-like growth factor receptor binding / growth factor activity / protein catabolic process / insulin receptor binding / hormone activity / antigen processing and presentation of endogenous peptide antigen via MHC class I / metalloendopeptidase activity / osteoblast differentiation / positive regulation of protein catabolic process / peroxisome / glucose metabolic process / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of peptidyl-tyrosine phosphorylation / integrin binding / positive regulation of protein binding / Platelet degranulation / insulin receptor signaling pathway / virus receptor activity / basolateral plasma membrane / endopeptidase activity / in utero embryonic development / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor ligand activity / Ub-specific processing proteases / external side of plasma membrane / positive regulation of cell population proliferation / regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / cell surface / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / mitochondrion / proteolysis / extracellular space / zinc ion binding / extracellular exosome / extracellular region / ATP binding / identical protein binding / nucleus / cytoplasm / cytosol
Similarity search - Function
Insulin-like growth factor II E-peptide, C-terminal / Insulin-like growth factor II / Insulin-like growth factor II E-peptide / Insulin-like growth factor / Peptidase M16, middle/third domain / Middle or third domain of peptidase_M16 / Cytochrome Bc1 Complex; Chain A, domain 1 / Metalloenzyme, LuxS/M16 peptidase-like / Peptidase M16, zinc-binding site / Insulinase family, zinc-binding region signature. ...Insulin-like growth factor II E-peptide, C-terminal / Insulin-like growth factor II / Insulin-like growth factor II E-peptide / Insulin-like growth factor / Peptidase M16, middle/third domain / Middle or third domain of peptidase_M16 / Cytochrome Bc1 Complex; Chain A, domain 1 / Metalloenzyme, LuxS/M16 peptidase-like / 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 / Insulin family / Insulin/IGF/Relaxin family / Insulin, conserved site / Insulin family signature. / Insulin-like / Insulin / insulin-like growth factor / relaxin family. / Insulin-like superfamily / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Insulin-like growth factor II / Insulin-degrading enzyme / Insulin-degrading enzyme
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.28 Å
AuthorsGuo, Q. / Manolopoulou, M. / Tang, W.-J.
CitationJournal: J.Mol.Biol. / Year: 2010
Title: Molecular Basis for the Recognition and Cleavages of IGF-II, TGF-alpha, and Amylin by Human Insulin-Degrading Enzyme.
Authors: Guo, Q. / Manolopoulou, M. / Bian, Y. / Schilling, A.B. / Tang, W.J.
History
DepositionAug 12, 2008Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 18, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Oct 20, 2021Group: Database references / Derived calculations
Category: database_2 / struct_conn ...database_2 / struct_conn / 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_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.3Feb 21, 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: Insulin-like growth factor II
D: Insulin-like growth factor II
hetero molecules


Theoretical massNumber of molelcules
Total (without water)244,2176
Polymers244,0864
Non-polymers1312
Water13,043724
1
A: Insulin-degrading enzyme
C: Insulin-like growth factor II
hetero molecules


Theoretical massNumber of molelcules
Total (without water)122,1093
Polymers122,0432
Non-polymers651
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1830 Å2
ΔGint-45 kcal/mol
Surface area37890 Å2
MethodPISA
2
B: Insulin-degrading enzyme
D: Insulin-like growth factor II
hetero molecules


Theoretical massNumber of molelcules
Total (without water)122,1093
Polymers122,0432
Non-polymers651
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1760 Å2
ΔGint-48 kcal/mol
Surface area38020 Å2
MethodPISA
Unit cell
Length a, b, c (Å)263.033, 263.033, 90.816
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number170
Space group name H-MP65

-
Components

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


Mass: 114558.656 Da / Num. of mol.: 2 / Fragment: UNP residues 42-1019
Mutation: C110L, E111Q, C171S, C178A, C257V, C414L, C573N, C590S, C789S, C812A, C819A, C904S, W908Y
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Strain: BL21(DE3)pUBS520 / Gene: IDE / Production host: Escherichia coli (E. coli)
References: UniProt: Q5T5N2, UniProt: P14735*PLUS, insulysin
#2: Protein Insulin-like growth factor II / IGF-II / Somatomedin-A


Mass: 7484.472 Da / Num. of mol.: 2 / Fragment: UNP residues 25-91
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: IGF2 / Production host: Escherichia coli (E. coli) / References: UniProt: P01344
#3: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 724 / 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: 3.93 Å3/Da / Density % sol: 68.68 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 10-13% PEG MME 5000, 100 mM HEPES pH 7.0, 4-14% Tacsimate, 10% dioxane, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 298 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 1.0003
DetectorType: MAR scanner 345 mm plate / Detector: IMAGE PLATE / Date: Jan 1, 2007
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0003 Å / Relative weight: 1
ReflectionResolution: 2.28→50 Å / Num. all: 162414 / Num. obs: 162414 / % possible obs: 99.9 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 5.4 % / Biso Wilson estimate: 13.4 Å2 / Rmerge(I) obs: 0.134 / Rsym value: 0.105 / Net I/σ(I): 20.1
Reflection shellResolution: 2.28→2.36 Å / Redundancy: 3.1 % / Rmerge(I) obs: 0.507 / Mean I/σ(I) obs: 2.1 / Num. unique all: 15661 / Rsym value: 0.539 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
REFMAC5.2.0019refinement
HKL-2000data collection
HKL-2000data reduction
SCALEPACKdata scaling
PHASESphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.28→50 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.933 / SU B: 5.023 / SU ML: 0.123 / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / ESU R: 0.196 / ESU R Free: 0.174 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.22983 8139 5 %RANDOM
Rwork0.19577 ---
obs0.19746 154214 99.71 %-
all-162414 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 36.385 Å2
Baniso -1Baniso -2Baniso -3
1--0.27 Å2-0.14 Å2-0 Å2
2---0.27 Å20 Å2
3---0.41 Å2
Refinement stepCycle: LAST / Resolution: 2.28→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms15685 0 2 724 16411
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.02216066
X-RAY DIFFRACTIONr_angle_refined_deg1.3361.96821728
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.85951912
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.82124.548796
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.664152878
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.8431582
X-RAY DIFFRACTIONr_chiral_restr0.0950.22349
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0212222
X-RAY DIFFRACTIONr_nbd_refined0.2070.27454
X-RAY DIFFRACTIONr_nbtor_refined0.3050.210882
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1510.2836
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.2540.250
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.3110.29
X-RAY DIFFRACTIONr_mcbond_it0.6951.59909
X-RAY DIFFRACTIONr_mcangle_it1.153215562
X-RAY DIFFRACTIONr_scbond_it1.95736962
X-RAY DIFFRACTIONr_scangle_it3.1634.56166
LS refinement shellResolution: 2.28→2.341 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.309 624 -
Rwork0.257 10933 -
obs--96.61 %

+
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