[English] 日本語
Yorodumi
- PDB-6xdd: Crystal structure of IRE1 in complex with G-3053 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6xdd
TitleCrystal structure of IRE1 in complex with G-3053
ComponentsSerine/threonine-protein kinase/endoribonuclease IRE1
KeywordsTRANSFERASE/INHIBITOR / KInase / RNase / inhibitor / 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 / peptidyl-serine autophosphorylation / IRE1-RACK1-PP2A complex / 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 / peptidyl-serine autophosphorylation / IRE1-RACK1-PP2A complex / platelet-derived growth factor receptor binding / positive regulation of endoplasmic reticulum unfolded protein response / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / nuclear inner membrane / endothelial cell proliferation / IRE1-mediated unfolded protein response / mRNA catabolic process / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / cellular response to vascular endothelial growth factor stimulus / cellular response to unfolded protein / regulation of macroautophagy / positive regulation of JUN kinase activity / positive regulation of vascular associated smooth muscle cell proliferation / Hsp70 protein binding / RNA endonuclease activity / response to endoplasmic reticulum stress / positive regulation of RNA splicing / cellular response to glucose stimulus / ADP binding / Hsp90 protein binding / cellular response to hydrogen peroxide / unfolded protein binding / protein autophosphorylation / 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 / WD40/YVTN repeat-like-containing domain superfamily / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Chem-N97 / Serine/threonine-protein kinase/endoribonuclease IRE1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å
AuthorsAckerly-Wallweber, H. / Wang, W.
CitationJournal: Acs Med.Chem.Lett. / Year: 2020
Title: Identification of BRaf-Sparing Amino-Thienopyrimidines with Potent IRE1 alpha Inhibitory Activity.
Authors: Beveridge, R.E. / Wallweber, H.A. / Ashkenazi, A. / Beresini, M. / Clark, K.R. / Gibbons, P. / Ghiro, E. / Kaufman, S. / Larivee, A. / Leblanc, M. / Leclerc, J.P. / Lemire, A. / Ly, C. / ...Authors: Beveridge, R.E. / Wallweber, H.A. / Ashkenazi, A. / Beresini, M. / Clark, K.R. / Gibbons, P. / Ghiro, E. / Kaufman, S. / Larivee, A. / Leblanc, M. / Leclerc, J.P. / Lemire, A. / Ly, C. / Rudolph, J. / Schwarz, J.B. / Srivastava, S. / Wang, W. / Zhao, L. / Braun, M.G.
History
DepositionJun 10, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 21, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 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
Revision 1.2Nov 20, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)100,8254
Polymers99,6032
Non-polymers1,2222
Water55831
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: cross-linking
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2710 Å2
ΔGint11 kcal/mol
Surface area38310 Å2
2
A: Serine/threonine-protein kinase/endoribonuclease IRE1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)50,4122
Polymers49,8011
Non-polymers6111
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
B: Serine/threonine-protein kinase/endoribonuclease IRE1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)50,4122
Polymers49,8011
Non-polymers6111
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)47.201, 156.816, 157.766
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

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


Mass: 49801.430 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ERN1, IRE1 / 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-N97 / 4-[(trans-4-aminocyclohexyl)amino]-N-(6-chloro-3-{[(2,5-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)thieno[3,2-d]pyrimidine-7-carboxamide


Mass: 611.059 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C25H22ClF3N6O3S2 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 31 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.93 Å3/Da / Density % sol: 58.04 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop
Details: 10% 2-propanol, 0.1 M sodium citrate tribasic dihydrate pH 5.0, and 26% PEG400, 4% pentaerythritol ethoxylate (3/4 EO/OH), 4% 1,3-Propanediol

-
Data collection

DiffractionMean temperature: 93 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL12-2 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Nov 29, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.4→49.62 Å / Num. obs: 45858 / % possible obs: 97.7 % / Redundancy: 6.6 % / Biso Wilson estimate: 55.21 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.056 / Rpim(I) all: 0.024 / Rrim(I) all: 0.061 / Net I/σ(I): 19.2
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
2.4-2.5370.6754685667380.9090.2750.732.4100
7.59-49.625.80.022961316630.9990.010.02459.599.5

-
Processing

Software
NameVersionClassification
Aimless0.5.28data scaling
PHENIX1.12-2829_finalrefinement
PDB_EXTRACT3.25data extraction
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6URC

6urc


Resolution: 2.4→49.619 Å / SU ML: 0.3 / Cross valid method: THROUGHOUT / σ(F): 1.26 / Phase error: 25.66 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2381 4057 4.71 %
Rwork0.1984 82054 -
obs0.2002 45769 97.32 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 142.87 Å2 / Biso mean: 63.8392 Å2 / Biso min: 34.28 Å2
Refinement stepCycle: final / Resolution: 2.4→49.619 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6560 0 80 31 6671
Biso mean--62.8 52.14 -
Num. residues----808
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0056808
X-RAY DIFFRACTIONf_angle_d0.7739210
X-RAY DIFFRACTIONf_chiral_restr0.048976
X-RAY DIFFRACTIONf_plane_restr0.0051182
X-RAY DIFFRACTIONf_dihedral_angle_d16.3394074
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.4-2.42830.30921210.28432886100
2.4283-2.45790.27831180.27292989100
2.4579-2.4890.30181740.26072919100
2.489-2.52180.26211260.25312840100
2.5218-2.55630.2991670.26152920100
2.5563-2.59280.27721120.2552921100
2.5928-2.63150.3031600.2592893100
2.6315-2.67260.33861420.2517234696
2.6726-2.71640.27021270.2551237496
2.7164-2.76330.33731770.26332900100
2.7633-2.81350.2661560.2387286799
2.8135-2.86760.29411580.2353285199
2.8676-2.92620.31781090.2445293899
2.9262-2.98980.32691640.23572851100
2.9898-3.05930.32341370.24912914100
3.0593-3.13580.2261170.2282957100
3.1358-3.22060.29591330.23552878100
3.2206-3.31530.26871910.25212854100
3.3153-3.42230.3261810.22872889100
3.4223-3.54460.28681240.2135242085
3.5446-3.68650.23551370.2029292299
3.6865-3.85420.24711480.1901286099
3.8542-4.05730.199870.1787243983
4.0573-4.31140.1961480.16222929100
4.3114-4.6440.20971380.14632886100
4.644-5.1110.1941290.15392894100
5.111-5.84950.17151090.1776293299
5.8495-7.36590.15611120.18662901100
7.3659-49.6190.19751550.1659288499
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)
11.7402-0.27830.21561.315-0.89991.2484-0.1616-0.8175-0.06610.54570.12520.0378-0.1772-0.0444-00.60860.0196-0.01670.82790.16370.6396-3.9371-22.783677.3352
21.58740.15150.72383.90170.27452.8264-0.028-0.296-0.00690.3111-0.0572-0.0287-0.58330.034900.5421-0.0449-0.05350.58410.06690.5133-6.2977-0.320568.0839
33.14580.5638-0.00262.34570.14142.58680.1453-0.06680.08420.0396-0.13150.0577-0.1204-0.20420.00010.6226-0.0179-0.02540.44820.03040.4771-4.492215.161639.1107
41.58320.46020.16371.8656-0.66142.2472-0.1987-0.2446-0.6558-0.28990.136-0.2430.70340.1767-0.00030.5668-0.00670.03820.67070.13050.6815-11.782-38.715562.4116
52.0842-0.6107-0.04823.60170.12633.43070.05730.021-0.1561-0.51170.0090.09920.0851-0.12440.00010.4104-0.0993-0.01750.43540.04040.4979-11.0304-30.684438.5466
62.8562-0.20130.14292.9911-0.1261.83810.14740.14140.0534-0.2364-0.0946-0.113-0.00010.02880.00010.60850.0032-0.00660.4650.04550.4707-13.7758-2.499922.626
70.4070.3911-0.04940.3402-0.01890.07060.0234-0.14860.00790.032-0.04280.1236-0.0286-0.2021-0.00020.3736-0.00280.00180.40930.10360.3744-6.4788-14.155551.6417
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain A and resi 560:644A560 - 963
2X-RAY DIFFRACTION2(chain A and resi 645:832) or (chain L and resi 1)A560 - 963
3X-RAY DIFFRACTION2(chain A and resi 645:832) or (chain L and resi 1)L0
4X-RAY DIFFRACTION3(chain A and resi 833:970)A560 - 963
5X-RAY DIFFRACTION4chain B and resi 560:644B560 - 963
6X-RAY DIFFRACTION5(chain B and resi 645:832) or (chain L and resi 2)B560 - 963
7X-RAY DIFFRACTION5(chain B and resi 645:832) or (chain L and resi 2)L0
8X-RAY DIFFRACTION6(chain B and resi 833:970)B560 - 963
9X-RAY DIFFRACTION7(chain S or (chain L and resi 3:9))S0

+
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