[English] 日本語
Yorodumi
- PDB-5jgb: Crystal structure of human TAK1/TAB1 fusion protein in complex wi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5jgb
TitleCrystal structure of human TAK1/TAB1 fusion protein in complex with ligand 10
ComponentsTAK1 kinase - TAB1 chimera fusion protein
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / Transferase-Transferase inhibitor complex / TAK1-TAB1 kinase
Function / homology
Function and homology information


histone kinase activity / positive regulation of cGAS/STING signaling pathway / MAP kinase kinase kinase kinase activity / nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / linear polyubiquitin binding / interleukin-17A-mediated signaling pathway / cardiac septum development / I-kappaB phosphorylation / mitogen-activated protein kinase kinase kinase / interleukin-33-mediated signaling pathway ...histone kinase activity / positive regulation of cGAS/STING signaling pathway / MAP kinase kinase kinase kinase activity / nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / linear polyubiquitin binding / interleukin-17A-mediated signaling pathway / cardiac septum development / I-kappaB phosphorylation / mitogen-activated protein kinase kinase kinase / interleukin-33-mediated signaling pathway / toll-like receptor 3 signaling pathway / type II transforming growth factor beta receptor binding / TRIF-dependent toll-like receptor signaling pathway / activation of NF-kappaB-inducing kinase activity / coronary vasculature development / ATAC complex / cellular response to angiotensin / positive regulation of vascular associated smooth muscle cell migration / anoikis / aorta development / MyD88-dependent toll-like receptor signaling pathway / interleukin-1-mediated signaling pathway / toll-like receptor 4 signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / protein serine/threonine phosphatase activity / mitogen-activated protein kinase p38 binding / non-canonical NF-kappaB signal transduction / p38MAPK cascade / stimulatory C-type lectin receptor signaling pathway / Fc-epsilon receptor signaling pathway / positive regulation of macroautophagy / positive regulation of cell size / MAP kinase kinase kinase activity / MAP kinase activity / canonical NF-kappaB signal transduction / positive regulation of cell cycle / heart morphogenesis / protein serine/threonine kinase binding / stress-activated MAPK cascade / positive regulation of JUN kinase activity / JNK cascade / IRAK2 mediated activation of TAK1 complex / positive regulation of vascular associated smooth muscle cell proliferation / Alpha-protein kinase 1 signaling pathway / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / TICAM1,TRAF6-dependent induction of TAK1 complex / positive regulation of interleukin-2 production / TRAF6-mediated induction of TAK1 complex within TLR4 complex / protein serine/threonine kinase activator activity / transforming growth factor beta receptor signaling pathway / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / TNFR1-induced NF-kappa-B signaling pathway / activated TAK1 mediates p38 MAPK activation / Activation of NF-kappaB in B cells / lung development / TAK1-dependent IKK and NF-kappa-B activation / NOD1/2 Signaling Pathway / positive regulation of protein serine/threonine kinase activity / receptor tyrosine kinase binding / positive regulation of T cell cytokine production / CLEC7A (Dectin-1) signaling / transcription coactivator binding / FCERI mediated NF-kB activation / Interleukin-1 signaling / positive regulation of non-canonical NF-kappaB signal transduction / MAPK cascade / Downstream TCR signaling / Ca2+ pathway / cellular response to tumor necrosis factor / T cell receptor signaling pathway / cellular response to hypoxia / scaffold protein binding / DNA-binding transcription factor binding / positive regulation of canonical NF-kappaB signal transduction / in utero embryonic development / positive regulation of MAPK cascade / molecular adaptor activity / endosome membrane / Ub-specific processing proteases / nuclear speck / defense response to bacterium / inflammatory response / immune response / negative regulation of gene expression / protein serine kinase activity / protein serine/threonine kinase activity / ubiquitin protein ligase binding / protein-containing complex binding / endoplasmic reticulum membrane / SARS-CoV-2 activates/modulates innate and adaptive immune responses / magnesium ion binding / endoplasmic reticulum / protein-containing complex / ATP binding / identical protein binding / nucleus / plasma membrane / cytoplasm / cytosol
Similarity search - Function
Mitogen-activated protein (MAP) kinase kinase kinase 7 / : / Protein phosphatase 2C / Protein phosphatase 2C family / Serine/threonine phosphatases, family 2C, catalytic domain / PPM-type phosphatase domain profile. / PPM-type phosphatase-like domain / PPM-type phosphatase-like domain superfamily / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain ...Mitogen-activated protein (MAP) kinase kinase kinase 7 / : / Protein phosphatase 2C / Protein phosphatase 2C family / Serine/threonine phosphatases, family 2C, catalytic domain / PPM-type phosphatase domain profile. / PPM-type phosphatase-like domain / PPM-type phosphatase-like domain superfamily / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-6JV / Mitogen-activated protein kinase kinase kinase 7 / TGF-beta-activated kinase 1 and MAP3K7-binding protein 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.8 Å
AuthorsIrie, M. / Nakamura, M. / Fukami, T.A. / Matsuura, T. / Morishima, K.
CitationJournal: Bioorg.Med.Chem. / Year: 2016
Title: Discovery of a potent and highly selective transforming growth factor beta receptor-associated kinase 1 (TAK1) inhibitor by structure based drug design (SBDD)
Authors: Muraoka, T. / Ide, M. / Morikami, K. / Irie, M. / Nakamura, M. / Miura, T. / Kamikawa, T. / Nishihara, M. / Kashiwagi, H.
History
DepositionApr 20, 2016Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Jul 27, 2016Provider: repository / Type: Initial release
Revision 1.1Sep 7, 2016Group: Database references
Revision 1.2Nov 8, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / database_2 / pdbx_initial_refinement_model / pdbx_struct_oper_list
Item: _citation.journal_id_CSD / _database_2.pdbx_DOI ..._citation.journal_id_CSD / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_oper_list.symmetry_operation

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: TAK1 kinase - TAB1 chimera fusion protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,0162
Polymers35,5311
Non-polymers4851
Water59433
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area14190 Å2
Unit cell
Length a, b, c (Å)58.711, 134.970, 143.169
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number23
Space group name H-MI222

-
Components

#1: Protein TAK1 kinase - TAB1 chimera fusion protein


Mass: 35530.953 Da / Num. of mol.: 1 / Fragment: UNP residues 31-303,UNP residues 468-504
Source method: isolated from a genetically manipulated source
Details: fusion of Mitogen-activated protein kinase kinase kinase 7,TGF-beta-activated kinase 1 and MAP3K7-binding protein 1
Source: (gene. exp.) Homo sapiens (human) / Gene: MAP3K7, TAK1, TAB1, MAP3K7IP1 / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: O43318, UniProt: Q15750, mitogen-activated protein kinase kinase kinase
#2: Chemical ChemComp-6JV / N-(2-methoxy-4-{[3-(4-methylpiperazin-1-yl)propyl]carbamoyl}phenyl)-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidine-7-carboxamide


Mass: 484.571 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H28N6O4S
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 33 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.99 Å3/Da / Density % sol: 69.18 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.7
Details: 1.7M sodium potassium phosphate, 20%(v/v) Glycerol as cryoprotectant

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å
DetectorType: MARRESEARCH / Detector: CCD / Date: Jul 31, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.8→98 Å / Num. obs: 13809 / % possible obs: 95.7 % / Redundancy: 3.8 % / Rmerge(I) obs: 0.103 / Net I/av σ(I): 10.718 / Net I/σ(I): 8.4
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsDiffraction-ID% possible all
2.8-2.852.60.456150.4
2.85-2.92.70.4164.7
2.9-2.962.80.474177.4
2.96-3.0230.366188
3.02-3.083.10.383194.2
3.08-3.153.40.315197.2
3.15-3.233.70.262199.3
3.23-3.3240.267199.9
3.32-3.4240.211199.7
3.42-3.534.10.1621100
3.53-3.654.10.1361100
3.65-3.84.10.1171100
3.8-3.974.10.1199.7
3.97-4.184.10.0821100
4.18-4.444.10.07199.9
4.44-4.7940.066199.3
4.79-5.2740.066199.7
5.27-6.0340.065199.6
6.03-7.5940.05199.1
7.59-503.70.037197.3

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing
REFMAC5.8.0135refinement
PDB_EXTRACT3.2data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2EVA

2eva


Resolution: 2.8→71.58 Å / Cor.coef. Fo:Fc: 0.931 / Cor.coef. Fo:Fc free: 0.895 / SU B: 12.005 / SU ML: 0.227 / SU R Cruickshank DPI: 0.4794 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.479 / ESU R Free: 0.303 / Details: U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2437 688 5.1 %RANDOM
Rwork0.2006 ---
obs0.2026 12901 94.23 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 120.84 Å2 / Biso mean: 48.586 Å2 / Biso min: 16.9 Å2
Baniso -1Baniso -2Baniso -3
1-0.02 Å20 Å2-0 Å2
2---0 Å20 Å2
3----0.02 Å2
Refinement stepCycle: final / Resolution: 2.8→71.58 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2288 0 34 33 2355
Biso mean--65.18 36.26 -
Num. residues----295
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0192394
X-RAY DIFFRACTIONr_angle_refined_deg1.2061.9523258
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.8365293
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.99122.84295
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.81915367
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.2031514
X-RAY DIFFRACTIONr_chiral_restr0.0810.2347
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0211820
X-RAY DIFFRACTIONr_mcbond_it1.964.9931178
X-RAY DIFFRACTIONr_mcangle_it3.5917.4791469
X-RAY DIFFRACTIONr_scbond_it1.8844.9251215
LS refinement shellResolution: 2.8→2.873 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.293 37 -
Rwork0.313 570 -
all-607 -
obs--59.45 %

+
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://pdbjlvh1.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