[English] 日本語
Yorodumi
- PDB-6w3k: Structure of unphosphorylated human IRE1 bound to G-9807 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6w3k
TitleStructure of unphosphorylated human IRE1 bound to G-9807
ComponentsSerine/threonine-protein kinase/endoribonuclease IRE1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / Kinase / Inhibitor / allosteric activator / UPR / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


peptidyl-serine trans-autophosphorylation / mRNA splicing, via endonucleolytic cleavage and ligation / AIP1-IRE1 complex / Ire1 complex / IRE1alpha activates chaperones / IRE1-TRAF2-ASK1 complex / insulin metabolic process / positive regulation of endoplasmic reticulum unfolded protein response / peptidyl-serine autophosphorylation / platelet-derived growth factor receptor binding ...peptidyl-serine trans-autophosphorylation / mRNA splicing, via endonucleolytic cleavage and ligation / AIP1-IRE1 complex / Ire1 complex / IRE1alpha activates chaperones / IRE1-TRAF2-ASK1 complex / insulin metabolic process / positive regulation of endoplasmic reticulum unfolded protein response / peptidyl-serine autophosphorylation / platelet-derived growth factor receptor binding / IRE1-RACK1-PP2A complex / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / endothelial cell proliferation / nuclear inner membrane / IRE1-mediated unfolded protein response / mRNA catabolic process / positive regulation of JUN kinase activity / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / cellular response to vascular endothelial growth factor stimulus / regulation of macroautophagy / cellular response to unfolded protein / positive regulation of vascular associated smooth muscle cell proliferation / RNA endonuclease activity / Hsp70 protein binding / response to endoplasmic reticulum stress / positive regulation of RNA splicing / Hsp90 protein binding / cellular response to glucose stimulus / ADP binding / cellular response to hydrogen peroxide / unfolded protein binding / protein autophosphorylation / eukaryotic translation initiation factor 2alpha kinase activity / 3-phosphoinositide-dependent protein kinase activity / DNA-dependent protein kinase activity / ribosomal protein S6 kinase activity / histone H3S10 kinase activity / histone H2AXS139 kinase activity / histone H3S28 kinase activity / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H3T3 kinase activity / histone H2AS121 kinase activity / Rho-dependent protein serine/threonine kinase activity / histone H2BS36 kinase activity / histone H3S57 kinase activity / histone H2AT120 kinase activity / AMP-activated protein kinase activity / histone H2AS1 kinase activity / histone H3T6 kinase activity / histone H3T11 kinase activity / histone H3T45 kinase activity / non-specific serine/threonine protein kinase / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / endoplasmic reticulum membrane / enzyme binding / magnesium ion binding / endoplasmic reticulum / protein homodimerization activity / mitochondrion / ATP binding / identical protein binding / cytoplasm
Similarity search - Function
Serine/threonine-protein kinase/endoribonuclease IRE1/2-like / KEN domain / KEN domain superfamily / Ribonuclease 2-5A / KEN domain profile. / domain in protein kinases, N-glycanases and other nuclear proteins / Pyrrolo-quinoline quinone beta-propeller repeat / beta-propeller repeat / Quinoprotein alcohol dehydrogenase-like superfamily / Serine/threonine-protein kinase, active site ...Serine/threonine-protein kinase/endoribonuclease IRE1/2-like / KEN domain / KEN domain superfamily / Ribonuclease 2-5A / KEN domain profile. / domain in protein kinases, N-glycanases and other nuclear proteins / Pyrrolo-quinoline quinone beta-propeller repeat / beta-propeller repeat / Quinoprotein alcohol dehydrogenase-like superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / WD40/YVTN repeat-like-containing domain superfamily / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Chem-SJS / Serine/threonine-protein kinase/endoribonuclease IRE1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.08 Å
AuthorsLammens, A. / Wang, W. / Ferri, E. / Rudolph, J.
CitationJournal: Nat Commun / Year: 2020
Title: Activation of the IRE1 RNase through remodeling of the kinase front pocket by ATP-competitive ligands.
Authors: Ferri, E. / Le Thomas, A. / Wallweber, H.A. / Day, E.S. / Walters, B.T. / Kaufman, S.E. / Braun, M.G. / Clark, K.R. / Beresini, M.H. / Mortara, K. / Chen, Y.A. / Canter, B. / Phung, W. / ...Authors: Ferri, E. / Le Thomas, A. / Wallweber, H.A. / Day, E.S. / Walters, B.T. / Kaufman, S.E. / Braun, M.G. / Clark, K.R. / Beresini, M.H. / Mortara, K. / Chen, Y.A. / Canter, B. / Phung, W. / Liu, P.S. / Lammens, A. / Ashkenazi, A. / Rudolph, J. / Wang, W.
History
DepositionMar 9, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 9, 2020Provider: repository / Type: Initial release
Revision 1.1Dec 30, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2Jun 16, 2021Group: Derived calculations / Category: pdbx_struct_oper_list
Item: _pdbx_struct_oper_list.name / _pdbx_struct_oper_list.symmetry_operation ..._pdbx_struct_oper_list.name / _pdbx_struct_oper_list.symmetry_operation / _pdbx_struct_oper_list.vector[1] / _pdbx_struct_oper_list.vector[3]
Revision 1.3Oct 18, 2023Group: 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: Serine/threonine-protein kinase/endoribonuclease IRE1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)49,9862
Polymers49,5611
Non-polymers4241
Water2,306128
1
A: Serine/threonine-protein kinase/endoribonuclease IRE1
hetero molecules

A: Serine/threonine-protein kinase/endoribonuclease IRE1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)99,9724
Polymers99,1232
Non-polymers8492
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_454-x-1,y,-z-11
Unit cell
Length a, b, c (Å)73.513, 112.761, 67.892
Angle α, β, γ (deg.)90.000, 119.580, 90.000
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11A-1181-

HOH

21A-1217-

HOH

-
Components

#1: Protein Serine/threonine-protein kinase/endoribonuclease IRE1 / Endoplasmic reticulum-to-nucleus signaling 1 / Inositol-requiring protein 1 / hIRE1p / Ire1-alpha / IRE1a


Mass: 49561.496 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ERN1, IRE1 / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: O75460, non-specific serine/threonine protein kinase, Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters
#2: Chemical ChemComp-SJS / 4-[5-[2,6-bis(fluoranyl)phenyl]-2~{H}-pyrazolo[3,4-b]pyridin-3-yl]-2-(4-oxidanylpiperidin-1-yl)-1~{H}-pyrimidin-6-one


Mass: 424.403 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H18F2N6O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 128 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.47 Å3/Da / Density % sol: 50.18 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop
Details: 10% (v/v) isopropanol, 11% (w/v) PEG4000, 0.1 M Na-citrate, pH 5.6

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 17, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.932→55.614 Å / Num. obs: 27588 / % possible obs: 86.6 % / Redundancy: 2.9 % / Biso Wilson estimate: 40.86 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.058 / Rpim(I) all: 0.04 / Rrim(I) all: 0.071 / Net I/σ(I): 10.2 / Num. measured all: 80019
Reflection shell

Num. unique obs: 1379 / Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
1.932-2.0952.80.71938540.6070.50.881.233.8
5.673-55.6142.90.04140510.9950.0290.05125.194.8

-
Processing

Software
NameVersionClassification
Aimlessdata scaling
PHENIX1.12-2829_finalrefinement
PDB_EXTRACT3.25data extraction
MOSFLMdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5HGI

5hgi


Resolution: 2.08→55.614 Å / SU ML: 0.27 / Cross valid method: THROUGHOUT / σ(F): 1.37 / Phase error: 24.03
RfactorNum. reflection% reflection
Rfree0.2174 1257 4.74 %
Rwork0.1905 --
obs0.1918 26537 91.87 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 187.2 Å2 / Biso mean: 61.4903 Å2 / Biso min: 22.23 Å2
Refinement stepCycle: final / Resolution: 2.08→55.614 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3224 0 31 128 3383
Biso mean--48.66 54.38 -
Num. residues----398
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.57660.2724-0.71080.8766-0.83641.69910.2296-0.01110.97180.22880.11850.0461-0.924-0.14120.00070.72360.04570.07030.40630.01190.7311-22.72628.772-18.382
22.6649-0.5221-1.24271.9009-0.32653.34-0.0688-0.40510.0530.11160.0038-0.11240.03970.1584-0.00140.2511-0.0134-0.04120.3465-0.00930.2651-21.2536.296-8.366
31.8195-0.7085-1.54312.40381.13114.8955-0.5195-0.1443-1.03950.2836-0.3499-0.19611.39220.0106-0.08330.7549-0.050.25420.35490.08110.8456-23.605-24.032-17.012
40.9882-0.2868-0.48080.623-0.06591.0361-0.0187-0.0788-0.0678-0.0242-0.0220.0755-0.0519-0.02070.00010.3919-0.0038-0.01720.4708-0.02760.3456-24.3793.237-14.092
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1( CHAIN A AND RESID 562:644 )A562 - 644
2X-RAY DIFFRACTION2( CHAIN A AND ( RESID 645:832 OR RESID 1001:1001 ) )A645 - 832
3X-RAY DIFFRACTION2( CHAIN A AND ( RESID 645:832 OR RESID 1001:1001 ) )A1001
4X-RAY DIFFRACTION3( CHAIN A AND RESID 833:963 )A833 - 963
5X-RAY DIFFRACTION4( CHAIN A AND RESID 1101:1228 )A1101 - 1228

+
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