[English] 日本語
Yorodumi
- PDB-7bmk: ATP-Competitive Partial Antagonists-'PAIR's-Rheostatically Modula... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7bmk
TitleATP-Competitive Partial Antagonists-'PAIR's-Rheostatically Modulate IRE1alpha's Kinase Helix-alphaC to Segregate its RNase-Mediated Biological Outputs
ComponentsSerine/threonine-protein kinase/endoribonuclease IRE1
KeywordsUNKNOWN FUNCTION / Kinase / kinase inhibitor / transferase / transferase inhibitor
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 / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters ...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 / Hydrolases; Acting on ester bonds; Endoribonucleases producing 5'-phosphomonoesters / platelet-derived growth factor receptor binding / positive regulation of endoplasmic reticulum unfolded protein response / endothelial cell proliferation / nuclear inner membrane / IRE1-mediated unfolded protein response / mRNA catabolic process / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / regulation of macroautophagy / cellular response to vascular endothelial growth factor stimulus / cellular response to unfolded protein / positive regulation of JUN kinase activity / RNA endonuclease activity / positive regulation of vascular associated smooth muscle cell proliferation / Hsp70 protein binding / response to endoplasmic reticulum stress / positive regulation of RNA splicing / ADP binding / cellular response to glucose stimulus / 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 / magnesium ion binding / enzyme 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. / WD40/YVTN repeat-like-containing domain superfamily / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
DI(HYDROXYETHYL)ETHER / TRIETHYLENE GLYCOL / Chem-U4N / Serine/threonine-protein kinase/endoribonuclease IRE1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.85 Å
AuthorsFeldman, H.C. / Ghosh, R. / Auyeung, V. / Mueller, J.L. / Vidadala, V.N. / Olivier, A. / Backes, B.J. / Zikherman, J. / Papa, F.R. / Maly, D.J.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)R01DK100623 United States
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)U01DK123609 United States
CitationJournal: Nat.Chem.Biol. / Year: 2021
Title: ATP-competitive partial antagonists of the IRE1 alpha RNase segregate outputs of the UPR.
Authors: Feldman, H.C. / Ghosh, R. / Auyeung, V.C. / Mueller, J.L. / Kim, J.H. / Potter, Z.E. / Vidadala, V.N. / Perera, B.G.K. / Olivier, A. / Backes, B.J. / Zikherman, J. / Papa, F.R. / Maly, D.J.
History
DepositionJan 20, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 29, 2021Provider: repository / Type: Initial release
Revision 1.1Apr 13, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

-
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)102,91738
Polymers99,1252
Non-polymers3,79236
Water11,331629
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area10040 Å2
ΔGint90 kcal/mol
Surface area37090 Å2
MethodPISA
Unit cell
Length a, b, c (Å)164.903, 72.813, 119.239
Angle α, β, γ (deg.)90.000, 129.820, 90.000
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11A-1292-

HOH

Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B

NCS domain segments:
Dom-IDComponent-IDEns-IDRefine codeAuth asym-IDAuth seq-ID
1010A562 - 963
2010B562 - 963

-
Components

-
Protein , 1 types, 2 molecules AB

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


Mass: 49562.590 Da / Num. of mol.: 2 / Fragment: KINASE AND NUCLEASE DOMAIN
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

-
Non-polymers , 6 types, 665 molecules

#2: Chemical ChemComp-U4N / 2,2,2-tris(fluoranyl)-~{N}-[4-[3-[2-[[(3~{S})-piperidin-3-yl]amino]pyrimidin-4-yl]pyridin-2-yl]oxynaphthalen-1-yl]ethanesulfonamide


Mass: 558.575 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C26H25F3N6O3S
#3: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 10 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 19 / Source method: obtained synthetically / Formula: C2H6O2
#5: Chemical
ChemComp-PEG / DI(HYDROXYETHYL)ETHER / Diethylene glycol


Mass: 106.120 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C4H10O3
#6: Chemical ChemComp-PGE / TRIETHYLENE GLYCOL / Polyethylene glycol


Mass: 150.173 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H14O4
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 629 / 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: 3.01 Å3/Da / Density % sol: 59.16 %
Crystal growTemperature: 279 K / Method: vapor diffusion / pH: 6
Details: 10.00 %v/v 2-PropOH 13.00 %w/v PEG 4K 0.10 M Na3 Cit

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.999999701977 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Oct 31, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.999999701977 Å / Relative weight: 1
ReflectionResolution: 1.85→91.59 Å / Num. obs: 91213 / % possible obs: 98.1 % / Redundancy: 2.9 % / Rmerge(I) obs: 0.037 / Net I/σ(I): 17.89
Reflection shellResolution: 1.85→2.1 Å / Redundancy: 2.9 % / Rmerge(I) obs: 0.43 / Num. unique obs: 28858 / % possible all: 98.6

-
Processing

Software
NameVersionClassification
XDSdata reduction
XSCALEdata scaling
REFMAC5.8.0155refinement
PDB_EXTRACT3.27data extraction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: NONE

Resolution: 1.85→91.59 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.946 / SU B: 4.348 / SU ML: 0.106 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.127 / ESU R Free: 0.127 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.235 2411 2.6 %RANDOM
Rwork0.1911 ---
obs0.1922 88799 98.4 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 142.59 Å2 / Biso mean: 42.17 Å2 / Biso min: 15.21 Å2
Baniso -1Baniso -2Baniso -3
1-0.63 Å20 Å2-0.08 Å2
2---0.43 Å20 Å2
3----0.03 Å2
Refinement stepCycle: final / Resolution: 1.85→91.59 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6461 0 252 641 7354
Biso mean--57.12 46.25 -
Num. residues----798
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0196927
X-RAY DIFFRACTIONr_bond_other_d0.0050.026554
X-RAY DIFFRACTIONr_angle_refined_deg1.6231.989345
X-RAY DIFFRACTIONr_angle_other_deg1.303315068
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.2425847
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.70123.333321
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.688151134
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.9011550
X-RAY DIFFRACTIONr_chiral_restr0.1010.21002
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0217722
X-RAY DIFFRACTIONr_gen_planes_other0.0030.021622
Refine LS restraints NCS

Ens-ID: 1 / Number: 9320 / Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Rms dev position: 0.04 Å / Weight position: 0.05

Dom-IDAuth asym-ID
1A
2B
LS refinement shellResolution: 1.85→1.898 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.463 194 -
Rwork0.462 6585 -
all-6779 -
obs--99.08 %
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)
16.34380.3344-3.32050.7237-0.2174.7470.1240.11620.05160.1647-0.02150.2638-0.221-0.4745-0.10250.0887-0.02070.04050.0991-0.01110.2224.07-6.05342.289
23.22560.13681.01682.48040.69464.49070.08450.407-0.0958-0.23680.2087-0.26970.05160.6866-0.29330.02750.00260.01930.1599-0.07070.04752.888-2.61923.553
38.50940.241-2.26630.64790.26743.0630.0192-0.25440.298-0.0390.09480.3927-0.0683-0.4939-0.1140.12130.02070.04340.2480.06640.354-2.121-20.20726.302
42.43510.2345-0.06993.17210.7724.13720.05370.1212-0.068-0.01290.1662-0.47170.34850.373-0.21980.0921-0.02970.02210.1151-0.06850.089446.33-19.5214.869
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A561 - 645
2X-RAY DIFFRACTION2A831 - 963
3X-RAY DIFFRACTION3B562 - 645
4X-RAY DIFFRACTION4B831 - 963

+
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