[English] 日本語
Yorodumi
- PDB-4o91: Crystal Structure of type II inhibitor NG25 bound to TAK1-TAB1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4o91
TitleCrystal Structure of type II inhibitor NG25 bound to TAK1-TAB1
ComponentsMitogen-activated protein kinase kinase kinase 7/TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 chimera
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / Mitogen-activated protein kinase kinase kinase 7 / TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 chimera / Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway / TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


histone kinase activity / I-kappaB phosphorylation / nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / positive regulation of JUN kinase activity / linear polyubiquitin binding / interleukin-17A-mediated signaling pathway / MAP kinase kinase kinase kinase activity / mitogen-activated protein kinase kinase kinase / interleukin-33-mediated signaling pathway / toll-like receptor 3 signaling pathway ...histone kinase activity / I-kappaB phosphorylation / nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / positive regulation of JUN kinase activity / linear polyubiquitin binding / interleukin-17A-mediated signaling pathway / MAP kinase kinase kinase kinase activity / 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 / negative regulation of necroptotic process / ATAC complex / positive regulation of vascular associated smooth muscle cell migration / positive regulation of cGAS/STING signaling pathway / negative regulation of reactive oxygen species metabolic process / anoikis / interleukin-1-mediated signaling pathway / toll-like receptor 4 signaling pathway / serine/threonine protein kinase complex / mitogen-activated protein kinase p38 binding / MyD88-dependent toll-like receptor signaling pathway / non-canonical NF-kappaB signal transduction / stimulatory C-type lectin receptor signaling pathway / p38MAPK cascade / positive regulation of cell size / Fc-epsilon receptor signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / MAP kinase kinase activity / protein serine/threonine phosphatase activity / cellular response to angiotensin / positive regulation of macroautophagy / MAP kinase activity / regulation of MAPK cascade / stress-activated MAPK cascade / MAP kinase kinase kinase activity / transforming growth factor beta receptor signaling pathway / JNK cascade / positive regulation of vascular associated smooth muscle cell proliferation / canonical NF-kappaB signal transduction / positive regulation of interleukin-2 production / signal transduction in response to DNA damage / positive regulation of cell cycle / IRAK2 mediated activation of TAK1 complex / protein serine/threonine kinase activator activity / 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 / TRAF6-mediated induction of TAK1 complex within TLR4 complex / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / protein serine/threonine kinase binding / cellular response to tumor necrosis factor / TNFR1-induced NF-kappa-B signaling pathway / activated TAK1 mediates p38 MAPK activation / positive regulation of T cell cytokine production / bone development / positive regulation of non-canonical NF-kappaB signal transduction / Activation of NF-kappaB in B cells / receptor tyrosine kinase binding / NOD1/2 Signaling Pathway / TAK1-dependent IKK and NF-kappa-B activation / kinase activity / T cell receptor signaling pathway / CLEC7A (Dectin-1) signaling / osteoblast differentiation / FCERI mediated NF-kB activation / transcription coactivator binding / Interleukin-1 signaling / MAPK cascade / Downstream TCR signaling / scaffold protein binding / cellular response to hypoxia / Ca2+ pathway / DNA-binding transcription factor binding / molecular adaptor activity / defense response to bacterium / positive regulation of canonical NF-kappaB signal transduction / inflammatory response / postsynaptic density / endosome membrane / Ub-specific processing proteases / immune response / negative regulation of gene expression / protein serine kinase activity / ubiquitin protein ligase binding / protein serine/threonine kinase activity / endoplasmic reticulum membrane / protein-containing complex binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / magnesium ion binding / endoplasmic reticulum / ATP binding / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
: / : / MAP3K7 C-terminal coiled coil / 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 ...: / : / MAP3K7 C-terminal coiled coil / 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 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); 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-NG2 / 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: 2.393 Å
AuthorsGurbani, D. / Hunter, J.C. / Tan, L. / Westover, K.D.
CitationJournal: J.Med.Chem. / Year: 2015
Title: Discovery of Type II Inhibitors of TGF beta-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2).
Authors: Tan, L. / Nomanbhoy, T. / Gurbani, D. / Patricelli, M. / Hunter, J. / Geng, J. / Herhaus, L. / Zhang, J. / Pauls, E. / Ham, Y. / Choi, H.G. / Xie, T. / Deng, X. / Buhrlage, S.J. / Sim, T. / ...Authors: Tan, L. / Nomanbhoy, T. / Gurbani, D. / Patricelli, M. / Hunter, J. / Geng, J. / Herhaus, L. / Zhang, J. / Pauls, E. / Ham, Y. / Choi, H.G. / Xie, T. / Deng, X. / Buhrlage, S.J. / Sim, T. / Cohen, P. / Sapkota, G. / Westover, K.D. / Gray, N.S.
History
DepositionDec 31, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 30, 2014Provider: repository / Type: Initial release
Revision 1.1Oct 8, 2014Group: Database references
Revision 1.2Jan 28, 2015Group: Database references
Revision 1.3Aug 2, 2017Group: Refinement description / Source and taxonomy / Category: entity_src_gen / software
Revision 1.4Feb 28, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Mitogen-activated protein kinase kinase kinase 7/TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 chimera
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,0012
Polymers35,4641
Non-polymers5381
Water2,000111
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
A: Mitogen-activated protein kinase kinase kinase 7/TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 chimera
hetero molecules

A: Mitogen-activated protein kinase kinase kinase 7/TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 chimera
hetero molecules

A: Mitogen-activated protein kinase kinase kinase 7/TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 chimera
hetero molecules

A: Mitogen-activated protein kinase kinase kinase 7/TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 chimera
hetero molecules


Theoretical massNumber of molelcules
Total (without water)144,0068
Polymers141,8554
Non-polymers2,1504
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_545-x,-y-1,z1
crystal symmetry operation3_555-x,y,-z1
crystal symmetry operation4_545x,-y-1,-z1
Buried area4710 Å2
ΔGint-41 kcal/mol
Surface area52570 Å2
MethodPISA
Unit cell
Length a, b, c (Å)58.214, 132.905, 145.498
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number23
Space group name H-MI222

-
Components

#1: Protein Mitogen-activated protein kinase kinase kinase 7/TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 chimera


Mass: 35463.867 Da / Num. of mol.: 1
Fragment: KINASE DOMAIN OF TAK1 (UNP O43318 RESIDUES 31-303) AND RESIDUES 468-504 OF TAB1 (UNP Q15750)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAP3K7, MAP3K7 TAK1 TAB1 MAP3K7IP1, TAK1
Plasmid: Plasmid 30115: pFastBac His6 TEV LIC cloning vector (4B)
Cell line (production host): High Five / Production host: Trichoplusia ni (cabbage looper)
Strain (production host): High Five Cells (BTI-TN-5B1-4) clonal isolate derived from the parental Trichop ulsia ni cell line (cabbage looper ovary)
References: UniProt: O43318, UniProt: Q15750, mitogen-activated protein kinase kinase kinase
#2: Chemical ChemComp-NG2 / N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methyl-3-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)benzamide


Mass: 537.576 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C29H30F3N5O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 111 / 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: 3.97 Å3/Da / Density % sol: 69 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 0.65-0.75 M sodium citrate, 0.2 M NaCl, 0.1 M Tris, and 5mM adenosine. Adenosine bound TAK1-TAB1 crystals are backsoaked with inhibitor, pH 7.0, VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97926 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Dec 7, 2013
RadiationMonochromator: Rosenbaum-Rock high-resolution double-crystal monochromator
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97926 Å / Relative weight: 1
ReflectionResolution: 2.35→98.13 Å / Num. obs: 22365 / % possible obs: 98.4 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Rmerge(I) obs: 0.082

-
Processing

Software
NameVersionClassification
HKL-3000data collection
PHASERphasing
PHENIXversion 1.8.4-1496refinement
HKL-3000data reduction
HKL-3000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.393→35.254 Å / Cor.coef. Fo:Fc: 0.941 / Cor.coef. Fo:Fc free: 0.909 / SU ML: 0.26 / σ(F): 1.34 / Phase error: 27.54 / Stereochemistry target values: ML / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflection
Rfree0.2073 1121 5.01 %
Rwork0.1771 --
obs0.1786 22365 98.45 %
all-23480 -
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 68.84 Å2
Baniso -1Baniso -2Baniso -3
1--0.9 Å2-0 Å20 Å2
2---0.02 Å2-0 Å2
3---0.92 Å2
Refinement stepCycle: LAST / Resolution: 2.393→35.254 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2330 0 39 111 2480
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0072441
X-RAY DIFFRACTIONf_angle_d0.9983317
X-RAY DIFFRACTIONf_dihedral_angle_d13.039919
X-RAY DIFFRACTIONf_chiral_restr0.036343
X-RAY DIFFRACTIONf_plane_restr0.005422
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.3928-2.50170.32891340.27672499X-RAY DIFFRACTION95
2.5017-2.63350.28981400.23292592X-RAY DIFFRACTION97
2.6335-2.79840.26881380.20852608X-RAY DIFFRACTION98
2.7984-3.01440.24481390.19172664X-RAY DIFFRACTION100
3.0144-3.31760.24311410.19032660X-RAY DIFFRACTION100
3.3176-3.79710.21451390.172687X-RAY DIFFRACTION100
3.7971-4.78210.16231410.14852712X-RAY DIFFRACTION100
4.7821-35.25790.17431490.16722822X-RAY DIFFRACTION99

+
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