[English] 日本語
Yorodumi
- PDB-2ypu: human insulin degrading enzyme E111Q in complex with inhibitor co... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2ypu
Titlehuman insulin degrading enzyme E111Q in complex with inhibitor compound 41367
ComponentsINSULIN-DEGRADING ENZYME
KeywordsHYDROLASE / M16A METALLOPROTEASE
Function / homology
Function and homology information


insulysin / beta-endorphin binding / ubiquitin recycling / insulin catabolic process / insulin metabolic process / amyloid-beta clearance by cellular catabolic process / hormone catabolic process / bradykinin catabolic process / cytosolic proteasome complex / insulin binding ...insulysin / beta-endorphin binding / ubiquitin recycling / insulin catabolic process / insulin metabolic process / amyloid-beta clearance by cellular catabolic process / hormone catabolic process / bradykinin catabolic process / cytosolic proteasome complex / insulin binding / regulation of aerobic respiration / peptide catabolic process / amyloid-beta clearance / peroxisomal matrix / amyloid-beta metabolic process / positive regulation of protein binding / Insulin receptor recycling / negative regulation of proteolysis / peptide binding / proteolysis involved in protein catabolic process / Peroxisomal protein import / protein catabolic process / antigen processing and presentation of endogenous peptide antigen via MHC class I / metalloendopeptidase activity / positive regulation of protein catabolic process / insulin receptor signaling pathway / peroxisome / amyloid-beta binding / virus receptor activity / endopeptidase activity / basolateral plasma membrane / Ub-specific processing proteases / external side of plasma membrane / protein-containing complex binding / cell surface / protein homodimerization activity / ATP hydrolysis activity / mitochondrion / proteolysis / extracellular space / extracellular exosome / zinc ion binding / ATP binding / identical protein binding / nucleus / cytoplasm / cytosol
Similarity search - Function
Peptidase M16, middle/third domain / Middle or third domain of peptidase_M16 / : / PQQ synthase PqqF-like, C-terminal lobe domain 4 / : / 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, middle/third domain / Middle or third domain of peptidase_M16 / : / PQQ synthase PqqF-like, C-terminal lobe domain 4 / : / 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 / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-I41 / Insulin-degrading enzyme
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.8 Å
AuthorsGuo, Q. / Deprez-Poulain, R. / Deprez, B. / Tang, W.-J.
CitationJournal: Eur J Med Chem / Year: 2014
Title: Imidazole-Derived 2-[N-Carbamoylmethyl-Alkylamino]Acetic Acids,Substrate-Dependent Modulators of Insulin-Degrading Enzyme in Amyloid-Beta Hydrolysis
Authors: Charton, J. / Gauriot, M. / Guo, Q. / Hennuyer, N. / Marechal, X. / Dumont, J. / Hamdane, M. / Pottiez, V. / Landry, V. / Sperandio, O. / Flipo, M. / Buee, L. / Staels, B. / Leroux, F. / ...Authors: Charton, J. / Gauriot, M. / Guo, Q. / Hennuyer, N. / Marechal, X. / Dumont, J. / Hamdane, M. / Pottiez, V. / Landry, V. / Sperandio, O. / Flipo, M. / Buee, L. / Staels, B. / Leroux, F. / Tang, W.-J. / Deprez, B. / Deprez-Poulain, R.
History
DepositionNov 1, 2012Deposition site: PDBE / Processing site: PDBE
SupersessionNov 28, 2012ID: 2YB3
Revision 1.0Nov 28, 2012Provider: repository / Type: Initial release
Revision 1.1Apr 16, 2014Group: Database references
Revision 1.2Apr 30, 2014Group: Database references
Revision 1.3Dec 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _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_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_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: INSULIN-DEGRADING ENZYME
B: INSULIN-DEGRADING ENZYME
hetero molecules


Theoretical massNumber of molelcules
Total (without water)230,0016
Polymers229,1212
Non-polymers8804
Water5,260292
1
A: INSULIN-DEGRADING ENZYME
hetero molecules


Theoretical massNumber of molelcules
Total (without water)115,0003
Polymers114,5611
Non-polymers4402
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: INSULIN-DEGRADING ENZYME
hetero molecules


Theoretical massNumber of molelcules
Total (without water)115,0003
Polymers114,5611
Non-polymers4402
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)262.288, 262.288, 90.630
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 / ABETA-DEGRADING PROTEASE / INSULIN PROTEASE / INSULINASE / INSULYSIN


Mass: 114560.578 Da / Num. of mol.: 2 / Fragment: RESIDUES 42-1019 / Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PPROEX-1 / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / Variant (production host): ROSETTA / References: UniProt: P14735, insulysin
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-I41 / 2-[[2-[[(2S)-3-(3H-IMIDAZOL-4-YL)-1-METHOXY-1-OXO-PROPAN-2-YL]AMINO]-2-OXO-ETHYL]-(PHENYLMETHYL)AMINO]ETHANOIC ACID / COMPOUND 41367


Mass: 374.391 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C18H22N4O5
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 292 / 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 % / Description: NONE

-
Data collection

DiffractionMean temperature: 77 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.98
DetectorType: ADSC QUANTUM 315 / Detector: CCD
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.98 Å / Relative weight: 1
ReflectionResolution: 2.8→50 Å / Num. obs: 82996 / % possible obs: 98.4 % / Observed criterion σ(I): 2 / Redundancy: 3.7 % / Rmerge(I) obs: 0.11 / Net I/σ(I): 13.5
Reflection shellResolution: 2.8→2.9 Å / Redundancy: 3.7 % / Rmerge(I) obs: 0.34 / Mean I/σ(I) obs: 2 / % possible all: 99.4

-
Processing

Software
NameVersionClassification
REFMAC5.5.0102refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3CWW

3cww


Resolution: 2.8→50 Å / Cor.coef. Fo:Fc: 0.941 / Cor.coef. Fo:Fc free: 0.901 / SU B: 9.548 / SU ML: 0.19 / Cross valid method: THROUGHOUT / ESU R: 0.444 / ESU R Free: 0.281 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
RfactorNum. reflection% reflectionSelection details
Rfree0.22548 4382 5 %RANDOM
Rwork0.1726 ---
obs0.17522 82987 99.9 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parameters
Baniso -1Baniso -2Baniso -3
1-0.11 Å20.05 Å20 Å2
2--0.11 Å20 Å2
3----0.16 Å2
Refinement stepCycle: LAST / Resolution: 2.8→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms15526 0 56 292 15874
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0220.02215972
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.951.96821616
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.6551906
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.01424.462780
X-RAY DIFFRACTIONr_dihedral_angle_3_deg18.956152820
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.7131580
X-RAY DIFFRACTIONr_chiral_restr0.1250.22330
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.02112184
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.8271.59562
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.701215452
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it3.03936410
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it5.2414.56164
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.804→2.877 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.305 351 -
Rwork0.235 6000 -
obs--99.2 %

+
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