[English] 日本語
Yorodumi
- PDB-6ydx: Insulin-regulated aminopeptidase complexed with a macrocyclic pep... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ydx
TitleInsulin-regulated aminopeptidase complexed with a macrocyclic peptidic inhibitor
ComponentsLeucyl-cystinyl aminopeptidaseLeucyl/cystinyl aminopeptidase
KeywordsHYDROLASE / Aminopeptidase / Antigen presentation / Complex / IRAP
Function / homology
Function and homology information


cystinyl aminopeptidase / antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent / negative regulation of cold-induced thermogenesis / peptide catabolic process / metalloaminopeptidase activity / aminopeptidase activity / early endosome lumen / female pregnancy / Translocation of SLC2A4 (GLUT4) to the plasma membrane / Endosomal/Vacuolar pathway ...cystinyl aminopeptidase / antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent / negative regulation of cold-induced thermogenesis / peptide catabolic process / metalloaminopeptidase activity / aminopeptidase activity / early endosome lumen / female pregnancy / Translocation of SLC2A4 (GLUT4) to the plasma membrane / Endosomal/Vacuolar pathway / peptide binding / protein catabolic process / cytoplasmic vesicle membrane / regulation of blood pressure / protein polyubiquitination / metallopeptidase activity / Antigen processing: Ubiquitination & Proteasome degradation / cell-cell signaling / lysosomal membrane / perinuclear region of cytoplasm / signal transduction / proteolysis / zinc ion binding / extracellular region / membrane / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Aminopeptidase N-type / ERAP1-like C-terminal domain / ERAP1-like C-terminal domain / Aminopeptidase N-like , N-terminal domain / Peptidase M1, alanine aminopeptidase/leukotriene A4 hydrolase / Peptidase M1, membrane alanine aminopeptidase / Peptidase family M1 domain / Peptidase M1 N-terminal domain / Aminopeptidase N-like , N-terminal domain superfamliy / Peptidase M4/M1, CTD superfamily / Neutral zinc metallopeptidases, zinc-binding region signature.
Similarity search - Domain/homology
Chem-ONN / DI(HYDROXYETHYL)ETHER / TRIETHYLENE GLYCOL / PHOSPHATE ION / SUCCINIC ACID / Leucyl-cystinyl aminopeptidase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.2 Å
AuthorsMpakali, A. / Saridakis, E. / Giastas, P. / Stratikos, E.
Funding supportEuropean Union, Greece, 2items
OrganizationGrant numberCountry
European CommissioniNEXT 5589European Union
General Secretariat for Research and Technology (GSRT)INSPIRED MIS 5002550 Greece
CitationJournal: Acs Med.Chem.Lett. / Year: 2020
Title: Structural Basis of Inhibition of Insulin-Regulated Aminopeptidase by a Macrocyclic Peptidic Inhibitor.
Authors: Mpakali, A. / Saridakis, E. / Giastas, P. / Maben, Z. / Stern, L.J. / Larhed, M. / Hallberg, M. / Stratikos, E.
History
DepositionMar 21, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 22, 2020Provider: repository / Type: Initial release
Revision 2.0Jul 29, 2020Group: Atomic model / Data collection ...Atomic model / Data collection / Database references / Derived calculations / Structure summary
Category: atom_site / atom_site_anisotrop ...atom_site / atom_site_anisotrop / chem_comp / citation / citation_author / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / pdbx_struct_conn_angle / struct_asym / struct_conn / struct_site / struct_site_gen
Item: _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ..._atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_asym_id / _atom_site.auth_atom_id / _atom_site.auth_comp_id / _atom_site.auth_seq_id / _atom_site.label_alt_id / _atom_site.label_asym_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.label_entity_id / _atom_site.occupancy / _atom_site.pdbx_formal_charge / _atom_site.type_symbol / _atom_site_anisotrop.U[1][1] / _atom_site_anisotrop.U[1][2] / _atom_site_anisotrop.U[1][3] / _atom_site_anisotrop.U[2][2] / _atom_site_anisotrop.U[2][3] / _atom_site_anisotrop.U[3][3] / _atom_site_anisotrop.pdbx_auth_asym_id / _atom_site_anisotrop.pdbx_auth_atom_id / _atom_site_anisotrop.pdbx_auth_comp_id / _atom_site_anisotrop.pdbx_auth_seq_id / _atom_site_anisotrop.pdbx_label_alt_id / _atom_site_anisotrop.pdbx_label_asym_id / _atom_site_anisotrop.pdbx_label_atom_id / _atom_site_anisotrop.pdbx_label_comp_id / _atom_site_anisotrop.type_symbol / _chem_comp.name / _chem_comp.pdbx_synonyms / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _struct_conn.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_ptnr1_label_alt_id / _struct_conn.pdbx_role / _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
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 2.1Jan 24, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Leucyl-cystinyl aminopeptidase
B: Leucyl-cystinyl aminopeptidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)216,16933
Polymers208,4352
Non-polymers7,73331
Water50428
1
A: Leucyl-cystinyl aminopeptidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)108,49118
Polymers104,2181
Non-polymers4,27317
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Leucyl-cystinyl aminopeptidase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)107,67815
Polymers104,2181
Non-polymers3,46014
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)73.419, 118.631, 141.389
Angle α, β, γ (deg.)90.000, 102.767, 90.000
Int Tables number4
Space group name H-MP1211
Space group name HallP2yb
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-ID
11
21

NCS domain segments:
Dom-IDComponent-IDEns-IDSelection detailsAuth asym-IDAuth seq-ID
111(chain 'A' and ((resid 159 and (name N or name...A159 - 175
121(chain 'A' and ((resid 159 and (name N or name...A177 - 335
131(chain 'A' and ((resid 159 and (name N or name...A342 - 406
141(chain 'A' and ((resid 159 and (name N or name...A408 - 598
151(chain 'A' and ((resid 159 and (name N or name...A602 - 636
161(chain 'A' and ((resid 159 and (name N or name...A650 - 968
171(chain 'A' and ((resid 159 and (name N or name...A971 - 981
181(chain 'A' and ((resid 159 and (name N or name...A983 - 1025
191(chain 'A' and ((resid 159 and (name N or name...A1119 - 1120
1101(chain 'A' and ((resid 159 and (name N or name...A1125 - 1126
1111(chain 'A' and ((resid 159 and (name N or name...A1132
1121(chain 'A' and ((resid 159 and (name N or name...A1141
1131(chain 'A' and ((resid 159 and (name N or name...A1143
1141(chain 'A' and ((resid 159 and (name N or name...A1145
1151(chain 'A' and ((resid 159 and (name N or name...A1303
1161(chain 'A' and ((resid 159 and (name N or name...A1402
2171(chain 'B' and (resid 159 through 175 or resid 177...B159 - 175
2181(chain 'B' and (resid 159 through 175 or resid 177...B177 - 335
2191(chain 'B' and (resid 159 through 175 or resid 177...B342 - 406
2201(chain 'B' and (resid 159 through 175 or resid 177...B408 - 598
2211(chain 'B' and (resid 159 through 175 or resid 177...B602 - 636
2221(chain 'B' and (resid 159 through 175 or resid 177...B650 - 968
2231(chain 'B' and (resid 159 through 175 or resid 177...B971 - 981
2241(chain 'B' and (resid 159 through 175 or resid 177...B983 - 1025
2251(chain 'B' and (resid 159 through 175 or resid 177...B1117
2261(chain 'B' and (resid 159 through 175 or resid 177...B1119
2271(chain 'B' and (resid 159 through 175 or resid 177...B1121
2281(chain 'B' and (resid 159 through 175 or resid 177...B1136
2291(chain 'B' and (resid 159 through 175 or resid 177...B1140 - 1141
2301(chain 'B' and (resid 159 through 175 or resid 177...B1143
2311(chain 'B' and (resid 159 through 175 or resid 177...B1145 - 1146
2321(chain 'B' and (resid 159 through 175 or resid 177...B1403

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Leucyl-cystinyl aminopeptidase / Leucyl/cystinyl aminopeptidase / Cystinyl aminopeptidase / Insulin-regulated membrane aminopeptidase / Insulin-responsive ...Cystinyl aminopeptidase / Insulin-regulated membrane aminopeptidase / Insulin-responsive aminopeptidase / IRAP / Oxytocinase / OTase / Placental leucine aminopeptidase / P-LAP


Mass: 104217.711 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: LNPEP, OTASE / Production host: Homo sapiens (human) / References: UniProt: Q9UIQ6, cystinyl aminopeptidase

-
Sugars , 3 types, 17 molecules

#2: Polysaccharide
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 5
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}LINUCSPDB-CARE
#3: Polysaccharide beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5]/1-1-2/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{}}}}LINUCSPDB-CARE
#6: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 10
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

-
Non-polymers , 9 types, 42 molecules

#4: Chemical ChemComp-ONN / 2-[2-[[[(4~{R},8~{S},11~{S})-11-azanyl-8-[(4-hydroxyphenyl)methyl]-6,10-bis(oxidanylidene)-1,2-dithia-5,9-diazacyclotridec-4-yl]carbonylamino]methyl]phenyl]ethanoic acid


Mass: 560.685 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Formula: C26H32N4O6S2 / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Formula: Zn
#7: Chemical ChemComp-SIN / SUCCINIC ACID / Succinic acid


Mass: 118.088 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H6O4
#8: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C2H6O2
#9: Chemical ChemComp-PGE / TRIETHYLENE GLYCOL / Polyethylene glycol


Mass: 150.173 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: C6H14O4
#10: Chemical ChemComp-PG4 / TETRAETHYLENE GLYCOL / Polyethylene glycol


Mass: 194.226 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H18O5 / Comment: precipitant*YM
#11: Chemical ChemComp-PO4 / PHOSPHATE ION / Phosphate


Mass: 94.971 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: PO4
#12: Chemical ChemComp-PEG / DI(HYDROXYETHYL)ETHER / Diethylene glycol


Mass: 106.120 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H10O3
#13: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 28 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.88 Å3/Da / Density % sol: 57.31 %
Crystal growTemperature: 289 K / Method: vapor diffusion / pH: 5
Details: PEG 1500, SPG (succinic acid, phosphate, glycine) buffer

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: PETRA III, EMBL c/o DESY / Beamline: P13 (MX1) / Wavelength: 0.976 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 24, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.976 Å / Relative weight: 1
ReflectionResolution: 3.01→45.96 Å / Num. obs: 45866 / % possible obs: 69.74 % / Redundancy: 3 % / Biso Wilson estimate: 53.44 Å2 / CC1/2: 0.977 / CC star: 0.994 / Net I/σ(I): 3.55
Reflection shellResolution: 3.011→3.118 Å / Mean I/σ(I) obs: 0.43 / Num. unique obs: 240 / CC1/2: 0.153 / CC star: 0.515

-
Processing

Software
NameVersionClassification
PHENIX1.17.1_3660refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5MJ6

5mj6


Resolution: 3.2→45.96 Å / SU ML: 0.5034 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 32.9965
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.3142 1563 4.89 %
Rwork0.2769 30400 -
obs0.2774 31963 81.7 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 38.41 Å2
Refinement stepCycle: LAST / Resolution: 3.2→45.96 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms13669 0 499 28 14196
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.008314604
X-RAY DIFFRACTIONf_angle_d1.328219806
X-RAY DIFFRACTIONf_chiral_restr0.08962287
X-RAY DIFFRACTIONf_plane_restr0.01032438
X-RAY DIFFRACTIONf_dihedral_angle_d19.59655195
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.2-3.30.3816800.32441425X-RAY DIFFRACTION42.8
3.3-3.420.3396920.30721909X-RAY DIFFRACTION56.96
3.42-3.560.31741260.30392215X-RAY DIFFRACTION66.07
3.56-3.720.30191470.28972542X-RAY DIFFRACTION75.96
3.72-3.920.31011470.28472815X-RAY DIFFRACTION83.23
3.92-4.160.30831130.26733068X-RAY DIFFRACTION90.16
4.16-4.480.29741600.25333229X-RAY DIFFRACTION95.04
4.48-4.930.31022030.24393269X-RAY DIFFRACTION97.67
4.93-5.650.30641670.26443341X-RAY DIFFRACTION97.82
5.65-7.110.33821810.29133279X-RAY DIFFRACTION97.38
7.11-45.960.29811470.28223308X-RAY DIFFRACTION94.66

+
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