[English] 日本語
Yorodumi
- PDB-8r5e: JNK1 covalently bound to RU77 cyclohexenone based inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8r5e
TitleJNK1 covalently bound to RU77 cyclohexenone based inhibitor
ComponentsMitogen-activated protein kinase 8
KeywordsSIGNALING PROTEIN / MAPK / MAP kinase / Kinase / Inhibitor / Covalent Inhibitor / c-Jun N-terminal kinases
Function / homology
Function and homology information


JUN phosphorylation / positive regulation of cell killing / basal dendrite / Activation of BMF and translocation to mitochondria / Interleukin-38 signaling / positive regulation of establishment of protein localization to mitochondrion / JUN kinase activity / Activation of BIM and translocation to mitochondria / WNT5:FZD7-mediated leishmania damping / positive regulation of cyclase activity ...JUN phosphorylation / positive regulation of cell killing / basal dendrite / Activation of BMF and translocation to mitochondria / Interleukin-38 signaling / positive regulation of establishment of protein localization to mitochondrion / JUN kinase activity / Activation of BIM and translocation to mitochondria / WNT5:FZD7-mediated leishmania damping / positive regulation of cyclase activity / histone deacetylase regulator activity / NRAGE signals death through JNK / Activation of the AP-1 family of transcription factors / positive regulation of NLRP3 inflammasome complex assembly / Fc-epsilon receptor signaling pathway / positive regulation of protein metabolic process / energy homeostasis / peptidyl-threonine phosphorylation / mitogen-activated protein kinase / regulation of macroautophagy / response to mechanical stimulus / negative regulation of protein binding / response to UV / stress-activated MAPK cascade / NRIF signals cell death from the nucleus / JNK cascade / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / protein serine/threonine kinase binding / cellular response to amino acid starvation / cellular response to reactive oxygen species / FCERI mediated MAPK activation / cellular response to mechanical stimulus / regulation of circadian rhythm / peptidyl-serine phosphorylation / histone deacetylase binding / Signaling by ALK fusions and activated point mutants / cellular senescence / rhythmic process / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / MAPK cascade / regulation of protein localization / cellular response to lipopolysaccharide / cellular response to oxidative stress / response to oxidative stress / Oxidative Stress Induced Senescence / protein phosphatase binding / protein phosphorylation / positive regulation of apoptotic process / axon / protein serine kinase activity / protein serine/threonine kinase activity / synapse / positive regulation of gene expression / negative regulation of apoptotic process / enzyme binding / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Mitogen-activated protein (MAP) kinase, JNK / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / : / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / 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
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / : / Mitogen-activated protein kinase 8
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.7 Å
AuthorsSok, P. / Poti, A. / Remenyi, A.
Funding support Hungary, 1items
OrganizationGrant numberCountry
Hungarian National Research, Development and Innovation OfficeKKP 126963 Hungary
CitationJournal: To Be Published
Title: The covalent coordination of cyclohexenone inhibitors in the MAP kinase docking groove
Authors: Poti, A. / Sok, P. / Remenyi, A.
History
DepositionNov 16, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 27, 2024Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Mitogen-activated protein kinase 8
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,9505
Polymers42,0331
Non-polymers9174
Water2,162120
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: isothermal titration calorimetry, JNK 163CYS is covalently linked to RU77 C3 carbon atom
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1140 Å2
ΔGint-12 kcal/mol
Surface area16770 Å2
Unit cell
Length a, b, c (Å)65.341, 75.249, 82.869
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Mitogen-activated protein kinase 8 / MAP kinase 8 / MAPK 8 / JNK-46 / Stress-activated protein kinase 1c / SAPK1c / Stress-activated ...MAP kinase 8 / MAPK 8 / JNK-46 / Stress-activated protein kinase 1c / SAPK1c / Stress-activated protein kinase JNK1 / c-Jun N-terminal kinase 1


Mass: 42032.566 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: The dephosphorylated inactive JNK1-beta-1 kinase with RU77 covalent inhibitor at the kinase docking groove
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK8, JNK1, PRKM8, SAPK1, SAPK1C / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P45983, mitogen-activated protein kinase

-
Non-polymers , 5 types, 124 molecules

#2: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#3: Chemical ChemComp-ANP / PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER


Mass: 506.196 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H17N6O12P3 / Comment: AMP-PNP, energy-carrying molecule analogue*YM
#4: Chemical ChemComp-Y6K / ~{O}3-~{tert}-butyl ~{O}1-methyl (1~{S},3~{R},5~{R})-6-methylidene-4-oxidanylidene-bicyclo[3.2.1]octane-1,3-dicarboxylate


Mass: 294.343 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H22O5 / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 120 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.42 Å3/Da / Density % sol: 49.18 % / Description: Long rods
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 8% PEG 20000 , 0,1 M HEPES pH 7.5, 10% MPD, and as reservoir 1.25 M NaCl was used

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: PETRA III, EMBL c/o DESY / Beamline: P14 (MX2) / Wavelength: 0.9763 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Oct 23, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9763 Å / Relative weight: 1
ReflectionResolution: 1.697→65.341 Å / Num. obs: 34746 / % possible obs: 94.6 % / Redundancy: 9.3 % / CC1/2: 1 / Rmerge(I) obs: 0.053 / Rpim(I) all: 0.026 / Rrim(I) all: 0.06 / Net I/σ(I): 22.1
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsCC1/2% possible all
1.697-1.8488.11.3531.71217370.761167.6
1.848-1.9129.752.20717380.79276.15
1.912-1.9619.872.43817370.824688.3

-
Processing

Software
NameVersionClassification
REFMAC5.8.0419refinement
STARANISOdata scaling
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.7→55.77 Å / Cor.coef. Fo:Fc: 0.967 / Cor.coef. Fo:Fc free: 0.95 / SU B: 5.911 / SU ML: 0.092 / Cross valid method: THROUGHOUT / ESU R: 0.236 / ESU R Free: 0.128 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.22161 2001 5.8 %RANDOM
Rwork0.17449 ---
obs0.17719 32690 75.56 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 37.106 Å2
Baniso -1Baniso -2Baniso -3
1-0.23 Å20 Å2-0 Å2
2--0.07 Å2-0 Å2
3----0.29 Å2
Refinement stepCycle: 1 / Resolution: 1.7→55.77 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2844 0 59 120 3023
Refine LS restraintsType: r_bond_refined_d / Dev ideal: 0.007 / Dev ideal target: 0.012 / Number: 2993
LS refinement shellResolution: 1.7→1.741 Å
RfactorNum. reflection% reflection
Rfree0.552 10 -
Rwork0.351 161 -
obs--5.12 %

+
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