[English] 日本語
Yorodumi
- PDB-4l52: Crystal Structure of 1-(4-{4-[7-amino-2-(1,2,3-benzothiadiazol-7-... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4l52
TitleCrystal Structure of 1-(4-{4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethan-1-one 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 / TAK1 kinase / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / positive regulation of cGAS/STING signaling pathway / histone kinase activity / MAP kinase kinase kinase kinase activity / 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 ...nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / positive regulation of cGAS/STING signaling pathway / histone kinase activity / MAP kinase kinase kinase kinase activity / 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 phosphatase activity / protein serine/threonine kinase binding / 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 / enzyme activator activity / MAP kinase kinase kinase activity / MAP kinase activity / canonical NF-kappaB signal transduction / stress-activated MAPK cascade / positive regulation of cell cycle / 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 / TRAF6-mediated induction of TAK1 complex within TLR4 complex / positive regulation of interleukin-2 production / 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 / transcription coactivator binding / receptor tyrosine kinase binding / CLEC7A (Dectin-1) signaling / positive regulation of T cell cytokine production / 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 / cellular response to hypoxia / T cell receptor signaling pathway / scaffold protein binding / positive regulation of canonical NF-kappaB signal transduction / DNA-binding transcription factor binding / in utero embryonic development / positive regulation of MAPK cascade / molecular adaptor activity / endosome membrane / Ub-specific processing proteases / nuclear speck / defense response to bacterium / immune response / inflammatory 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-1UL / 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 / Resolution: 2.54 Å
AuthorsWang, J. / Hornberger, K.R. / Crew, A.P. / Jestel, A. / Maskos, K. / Moertl, M.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2013
Title: Discovery and optimization of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1.
Authors: Hornberger, K.R. / Berger, D.M. / Crew, A.P. / Dong, H. / Kleinberg, A. / Li, A.H. / Medeiros, M.R. / Mulvihill, M.J. / Siu, K. / Tarrant, J. / Wang, J. / Weng, F. / Wilde, V.L. / ...Authors: Hornberger, K.R. / Berger, D.M. / Crew, A.P. / Dong, H. / Kleinberg, A. / Li, A.H. / Medeiros, M.R. / Mulvihill, M.J. / Siu, K. / Tarrant, J. / Wang, J. / Weng, F. / Wilde, V.L. / Albertella, M. / Bittner, M. / Cooke, A. / Gray, M.J. / Maresca, P. / May, E. / Meyn, P. / Peick, W. / Romashko, D. / Tanowitz, M. / Tokar, B.
History
DepositionJun 10, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 3, 2013Provider: repository / Type: Initial release
Revision 1.1Jul 31, 2013Group: Database references
Revision 1.2Aug 7, 2013Group: Database references
Revision 1.3Jul 26, 2017Group: Advisory / Refinement description / Source and taxonomy
Category: entity_src_gen / pdbx_unobs_or_zero_occ_atoms / software
Revision 1.4Nov 15, 2017Group: Refinement description / Category: software

-
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)35,1692
Polymers34,7091
Non-polymers4601
Water63135
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)58.160, 133.784, 142.237
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 / Tak1-Tab1 fusion protein / Transforming growth factor-beta-activated kinase 1 / TGF-beta-activated ...Tak1-Tab1 fusion protein / 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: 34709.043 Da / Num. of mol.: 1 / Fragment: SEE REMARK 999
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAP3K7, TAK1, MAP3K7IP1, TAB1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: O43318, UniProt: Q15750, mitogen-activated protein kinase kinase kinase
#2: Chemical ChemComp-1UL / 1-(4-{4-[7-amino-2-(1,2,3-benzothiadiazol-7-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone


Mass: 459.524 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H21N7O2S
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 35 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsPROTEIN IS A CHIMERA COMPRISING THE KINASE DOMAIN OF TAK1 (UNP O43318 RESIDUES 31-303) AND RESIDUES ...PROTEIN IS A CHIMERA COMPRISING THE KINASE DOMAIN OF TAK1 (UNP O43318 RESIDUES 31-303) AND RESIDUES 468-496 OF TAB1 (UNP Q15750).

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.99 Å3/Da / Density % sol: 69.14 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 0.75 M sodium citrate, 0.2 M sodium chloride, 0.1 M TRIS, pH 7.0, VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 29, 2010 / Details: dynamically bendable mirror
RadiationMonochromator: LN2 cooled fixed-exit Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.54→97.51 Å / Num. all: 18760 / Num. obs: 18760 / % possible obs: 93.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 3.4 % / Rmerge(I) obs: 0.059
Reflection shellResolution: 2.54→2.76 Å / Redundancy: 3.5 % / Rmerge(I) obs: 0.449 / % possible all: 95.9

-
Processing

Software
NameVersionClassification
MOLREPphasing
REFMAC5.2.0005refinement
XDSdata reduction
XSCALEdata scaling
RefinementResolution: 2.54→97.51 Å / Cor.coef. Fo:Fc: 0.952 / Cor.coef. Fo:Fc free: 0.94 / SU B: 16.314 / SU ML: 0.168 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.284 / ESU R Free: 0.224 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.22953 666 3.8 %RANDOM
Rwork0.19455 ---
all0.19584 16952 --
obs0.19584 16952 93.93 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 66.686 Å2
Baniso -1Baniso -2Baniso -3
1--5.32 Å20 Å20 Å2
2---2.52 Å20 Å2
3---7.84 Å2
Refinement stepCycle: LAST / Resolution: 2.54→97.51 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2341 0 33 35 2409
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0212380
X-RAY DIFFRACTIONr_bond_other_d0.0010.022101
X-RAY DIFFRACTIONr_angle_refined_deg1.4221.9643250
X-RAY DIFFRACTIONr_angle_other_deg0.79734857
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.5445295
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.6323.06198
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.54615349
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.9131514
X-RAY DIFFRACTIONr_chiral_restr0.0690.2341
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.022674
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02494
X-RAY DIFFRACTIONr_nbd_refined0.2180.2524
X-RAY DIFFRACTIONr_nbd_other0.1850.22090
X-RAY DIFFRACTIONr_nbtor_refined0.1880.21194
X-RAY DIFFRACTIONr_nbtor_other0.0890.21232
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.150.249
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.0890.211
X-RAY DIFFRACTIONr_symmetry_vdw_other0.1660.240
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.0150.23
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it2.43821884
X-RAY DIFFRACTIONr_mcbond_other0.4342594
X-RAY DIFFRACTIONr_mcangle_it2.99432378
X-RAY DIFFRACTIONr_scbond_it4.46141103
X-RAY DIFFRACTIONr_scangle_it6.2046872
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.54→2.606 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.415 49 -
Rwork0.31 1250 -
obs--96.01 %
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)
13.77794.0625-1.55157.3677-5.87216.52930.4772-0.8134-0.37391.1196-0.0305-0.01750.2322-0.3257-0.44660.5247-0.03610.00730.44220.05380.2092-8.585-50.504-8.096
23.5654-0.8899-0.20473.7535-0.22812.1241-0.0453-0.008-0.372-0.03120.0561-0.03390.2111-0.0395-0.0107-0.1167-0.0189-0.0041-0.09820.0552-0.1613-6.238-44.247-33.602
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A26 - 106
2X-RAY DIFFRACTION2A107 - 496

+
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