[English] 日本語
Yorodumi
- PDB-5e7r: Crystal structure of TL10-81 bound to TAK1-TAB1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5e7r
TitleCrystal structure of TL10-81 bound to TAK1-TAB1
ComponentsTAK1 kinase - TAB1 chimera fusion protein
KeywordsTRANSFERASE/TRANSFERASE inhibitor / Mitogen-activated protein kinase kinase kinase 7/TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 / TRANSFERASE-TRANSFERASE inhibitor complex
Function / homology
Function and homology information


positive regulation of cGAS/STING signaling pathway / histone kinase activity / 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 ...positive regulation of cGAS/STING signaling pathway / histone kinase activity / 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 / positive regulation of vascular associated smooth muscle cell migration / cellular response to angiotensin / anoikis / aorta development / MyD88-dependent toll-like receptor signaling pathway / interleukin-1-mediated signaling pathway / toll-like receptor 4 signaling pathway / protein serine/threonine kinase binding / protein serine/threonine phosphatase activity / mitogen-activated protein kinase p38 binding / cytoplasmic pattern recognition receptor signaling pathway / p38MAPK cascade / non-canonical NF-kappaB signal transduction / Fc-epsilon receptor signaling pathway / stimulatory C-type lectin 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 / enzyme activator activity / positive regulation of cell cycle / stress-activated MAPK cascade / heart morphogenesis / positive regulation of JUN kinase activity / JNK cascade / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / positive regulation of vascular associated smooth muscle cell proliferation / 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 / TAK1-dependent IKK and NF-kappa-B activation / lung development / 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 / cytosol / cytoplasm
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-5KW / 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 / Resolution: 2.11 Å
AuthorsGurbani, D. / Hunter, J.C. / Tan, L. / Chen, Z. / Westover, K.D.
Funding support United States, 1items
OrganizationGrant numberCountry
Cancer Prevention and Research Institute of Texas (CPRIT)CPRIT R1207 and CPRIT RP140233 United States
CitationJournal: Bioorg. Med. Chem. / Year: 2017
Title: Structure-guided development of covalent TAK1 inhibitors.
Authors: Tan, L. / Gurbani, D. / Weisberg, E.L. / Hunter, J.C. / Li, L. / Jones, D.S. / Ficarro, S.B. / Mowafy, S. / Tam, C.P. / Rao, S. / Du, G. / Griffin, J.D. / Sorger, P.K. / Marto, J.A. / Westover, K.D. / Gray, N.S.
History
DepositionOct 13, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 21, 2016Provider: repository / Type: Initial release
Revision 1.1Feb 15, 2017Group: Database references
Revision 1.2Sep 27, 2017Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Jan 8, 2020Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4Sep 27, 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: TAK1 kinase - TAB1 chimera fusion protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,9512
Polymers35,4641
Non-polymers4871
Water93752
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)58.179, 134.093, 149.044
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number23
Space group name H-MI222

-
Components

#1: Protein TAK1 kinase - TAB1 chimera fusion protein / Transforming growth factor-beta-activated kinase 1 / TGF-beta-activated kinase 1 / Mitogen- ...Transforming growth factor-beta-activated kinase 1 / TGF-beta-activated kinase 1 / Mitogen-activated protein kinase kinase kinase 7-interacting protein 1 / TGF-beta-activated kinase 1-binding protein 1 / TAK1-binding protein 1


Mass: 35463.867 Da / Num. of mol.: 1
Fragment: UNP O43318 residues 31-303, UNP Q15750 residues 468-504
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAP3K7, TAK1, TAB1, MAP3K7IP1 / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: O43318, UniProt: Q15750, mitogen-activated protein kinase kinase kinase
#2: Chemical ChemComp-5KW / 2-chloro-N-{2-[(5-chloro-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-4-yl)oxy]phenyl}acetamide


Mass: 487.382 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H24Cl2N6O2
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 52 / 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: 4.07 Å3/Da / Density % sol: 69.77 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 0.65-0.75 M sodium citrate pH 7.0, 0.2 M NaCl, 0.1 M Tris pH 7.0, and 5mM adenosine. Adenosine bound TAK1-TAB1 crystals are backsoaked with inhibitor

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97918 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Oct 16, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 2.1→50 Å / Num. obs: 32105 / % possible obs: 96.7 % / Redundancy: 8 % / Rmerge(I) obs: 0.235 / Rpim(I) all: 0.088 / Net I/σ(I): 6.3
Reflection shellResolution: 2.1→2.14 Å / Redundancy: 6.4 % / Mean I/σ(I) obs: 1.7 / CC1/2: 0.561 / Rpim(I) all: 0.553 / % possible all: 98.4

-
Processing

Software
NameVersionClassification
PHENIX(1.10_2155: ???)refinement
DENZOdata reduction
SCALEPACKdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2YIY

2yiy


Resolution: 2.11→42.148 Å / SU ML: 0.24 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 28.66 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2456 1282 4 %
Rwork0.22 --
obs0.221 32069 94.17 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.11→42.148 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2169 0 32 52 2253
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0072269
X-RAY DIFFRACTIONf_angle_d0.9563080
X-RAY DIFFRACTIONf_dihedral_angle_d13.3551342
X-RAY DIFFRACTIONf_chiral_restr0.05320
X-RAY DIFFRACTIONf_plane_restr0.007391
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.1096-2.19410.29111140.3152726X-RAY DIFFRACTION76
2.1941-2.29390.35591440.32693512X-RAY DIFFRACTION98
2.2939-2.41480.23961460.24853525X-RAY DIFFRACTION98
2.4148-2.56610.28321460.23923487X-RAY DIFFRACTION98
2.5661-2.76420.29131480.22643541X-RAY DIFFRACTION97
2.7642-3.04230.26991460.23563491X-RAY DIFFRACTION97
3.0423-3.48240.25591450.22883504X-RAY DIFFRACTION96
3.4824-4.38670.2071460.19453500X-RAY DIFFRACTION95
4.3867-42.15660.23051470.19743501X-RAY DIFFRACTION92

+
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