[English] 日本語
Yorodumi
- PDB-6bod: TBK1 in complex with ethyl ester analog of amlexanox -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6bod
TitleTBK1 in complex with ethyl ester analog of amlexanox
ComponentsSerine/threonine-protein kinase TBK1
KeywordsTRANSFERASE / TBK1 / kinase / amlexanox / obesity / diabetes
Function / homology
Function and homology information


IRF3 mediated activation of type 1 IFN / STAT6-mediated induction of chemokines / positive regulation of xenophagy / serine/threonine protein kinase complex / regulation of type I interferon production / dendritic cell proliferation / IRF3-mediated induction of type I IFN / positive regulation of type I interferon-mediated signaling pathway / Interleukin-37 signaling / TNFR1-induced proapoptotic signaling ...IRF3 mediated activation of type 1 IFN / STAT6-mediated induction of chemokines / positive regulation of xenophagy / serine/threonine protein kinase complex / regulation of type I interferon production / dendritic cell proliferation / IRF3-mediated induction of type I IFN / positive regulation of type I interferon-mediated signaling pathway / Interleukin-37 signaling / TNFR1-induced proapoptotic signaling / toll-like receptor 4 signaling pathway / TRAF6 mediated IRF7 activation / type I interferon-mediated signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / positive regulation of interferon-alpha production / antiviral innate immune response / positive regulation of macroautophagy / positive regulation of type I interferon production / canonical NF-kappaB signal transduction / positive regulation of autophagy / negative regulation of TORC1 signaling / positive regulation of TORC1 signaling / TICAM1-dependent activation of IRF3/IRF7 / Regulation of innate immune responses to cytosolic DNA / activation of innate immune response / positive regulation of interferon-beta production / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Negative regulators of DDX58/IFIH1 signaling / Regulation of TNFR1 signaling / phosphoprotein binding / peptidyl-threonine phosphorylation / response to virus / DDX58/IFIH1-mediated induction of interferon-alpha/beta / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of peptidyl-serine phosphorylation / TRAF3-dependent IRF activation pathway / peptidyl-serine phosphorylation / protein phosphatase binding / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / Potential therapeutics for SARS / nucleic acid binding / non-specific serine/threonine protein kinase / protein kinase activity / defense response to Gram-positive bacterium / inflammatory response / protein phosphorylation / negative regulation of gene expression / protein serine kinase activity / intracellular membrane-bounded organelle / innate immune response / protein serine/threonine kinase activity / SARS-CoV-2 activates/modulates innate and adaptive immune responses / positive regulation of transcription by RNA polymerase II / nucleoplasm / ATP binding / identical protein binding / cytosol / cytoplasm
Similarity search - Function
Substrate Binding Domain Of Dnak; Chain:A; Domain 2 - #420 / TANK binding kinase 1, ubiquitin-like domain / TANK-binding kinase 1, coiled-coil domain 1 / TANK-binding kinase 1 coiled-coil domain 1 / TANK binding kinase 1 ubiquitin-like domain / Substrate Binding Domain Of Dnak; Chain:A; Domain 2 / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 1 / Ubiquitin-like (UB roll) / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 ...Substrate Binding Domain Of Dnak; Chain:A; Domain 2 - #420 / TANK binding kinase 1, ubiquitin-like domain / TANK-binding kinase 1, coiled-coil domain 1 / TANK-binding kinase 1 coiled-coil domain 1 / TANK binding kinase 1 ubiquitin-like domain / Substrate Binding Domain Of Dnak; Chain:A; Domain 2 / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 1 / Ubiquitin-like (UB roll) / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Roll / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / Up-down Bundle / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-E0P / Serine/threonine-protein kinase TBK1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 3.197 Å
AuthorsBeyett, T.S. / Tesmer, J.J.G.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)R01 DK100319 United States
CitationJournal: Mol. Pharmacol. / Year: 2018
Title: Carboxylic Acid Derivatives of Amlexanox Display Enhanced Potency toward TBK1 and IKKepsilonand Reveal Mechanisms for Selective Inhibition.
Authors: Beyett, T.S. / Gan, X. / Reilly, S.M. / Chang, L. / Gomez, A.V. / Saltiel, A.R. / Showalter, H.D. / Tesmer, J.J.G.
History
DepositionNov 19, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 26, 2018Provider: repository / Type: Initial release
Revision 1.1Feb 20, 2019Group: Author supporting evidence / Data collection / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.2Dec 25, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Oct 4, 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: Serine/threonine-protein kinase TBK1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)76,3522
Polymers76,0261
Non-polymers3261
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area33220 Å2
Unit cell
Length a, b, c (Å)134.314, 134.314, 85.275
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number154
Space group name H-MP3221

-
Components

#1: Protein Serine/threonine-protein kinase TBK1 / NF-kappa-B-activating kinase / T2K / TANK-binding kinase 1


Mass: 76025.922 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TBK1, NAK / Plasmid: pH7pFB / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q9UHD2, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-E0P / ethyl 2-amino-5-oxo-7-(propan-2-yl)-5H-[1]benzopyrano[2,3-b]pyridine-3-carboxylate


Mass: 326.347 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H18N2O4

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.92 Å3/Da / Density % sol: 57.83 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 0.1 M HEPES pH 7.5, 4% PEG 8000 / PH range: 7.0-8.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-G / Wavelength: 0.97857 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Apr 12, 2017
RadiationMonochromator: Double Crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97857 Å / Relative weight: 1
ReflectionResolution: 3.2→48.048 Å / Num. obs: 14973 / % possible obs: 99.9 % / Redundancy: 16.401 % / Biso Wilson estimate: 121.78 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.11 / Rrim(I) all: 0.113 / Χ2: 1.002 / Net I/σ(I): 18.17 / Num. measured all: 245576
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
3.2-3.3916.7441.7171.9839818238223780.7131.77299.8
3.39-3.6217.0620.8614.1438219224022400.9190.888100
3.62-3.9116.9730.4028.5635270207820780.9820.414100
3.91-4.2816.9380.19315.6732808193719370.9960.199100
4.28-4.7816.5750.11124.5329022175117510.9980.115100
4.78-5.5116.2990.0929.4125475156315630.9980.093100
5.51-6.7315.7880.08631.5421077133513350.9980.088100
6.73-9.4315.050.04945.89158781055105510.051100
9.43-48.04812.5930.04448.05800964363610.04598.9

-
Phasing

PhasingMethod: molecular replacement
Phasing MR
Highest resolutionLowest resolution
Rotation7.48 Å68.69 Å
Translation7.48 Å68.69 Å

-
Processing

Software
NameVersionClassification
PHENIX1.11.1_2575refinement
XSCALE0.5.26data scaling
PHASER2.6.0phasing
PDB_EXTRACT3.22data extraction
Cootmodel building
XDSdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4IM0

4im0


Resolution: 3.197→48.048 Å / SU ML: 0.45 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 30.98 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.271 1497 9.97 %
Rwork0.2228 25513 -
obs0.2277 14927 99.59 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 282.68 Å2 / Biso mean: 141.9368 Å2 / Biso min: 69.1 Å2
Refinement stepCycle: final / Resolution: 3.197→48.048 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4936 0 24 0 4960
Biso mean--184.38 --
Num. residues----610
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0015062
X-RAY DIFFRACTIONf_angle_d0.3966835
X-RAY DIFFRACTIONf_chiral_restr0.038759
X-RAY DIFFRACTIONf_plane_restr0.003868
X-RAY DIFFRACTIONf_dihedral_angle_d8.493051
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 20

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
3.1974-3.25250.47381300.43541235136598
3.2525-3.31170.43561440.39312971441100
3.3117-3.37530.40551420.360912651407100
3.3753-3.44420.35411420.322413171459100
3.4442-3.51910.31041400.29512681408100
3.5191-3.60090.36261400.297212731413100
3.6009-3.69090.34071490.296412741423100
3.6909-3.79070.30581430.265412771420100
3.7907-3.90220.30681420.256912771419100
3.9022-4.02810.29711340.234112731407100
4.0281-4.1720.23641500.227612971447100
4.172-4.33890.25281460.219312771423100
4.3389-4.53620.29631450.222712691414100
4.5362-4.77520.25021360.210512841420100
4.7752-5.07410.23381400.198812821422100
5.0741-5.46540.30471480.226712831431100
5.4654-6.01440.26841480.248812631411100
6.0144-6.88250.29441340.244313011435100
6.8825-8.6630.2951400.177612721412100
8.663-48.05390.17211320.15611229136195
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)
14.85062.1133-2.29813.3754-0.19051.2525-0.29180.4097-0.3711-0.56380.1046-0.74930.23870.12860.16561.01550.14950.01881.25530.00251.3491-28.2411-14.74-4.468
25.9911-0.4468-1.59125.0314-3.16762.5920.10270.2659-1.2653-0.4314-0.20070.20411.15820.429-0.10531.1708-0.0058-0.05191.0238-0.06571.5995-33.6573-32.67887.7608
32.83430.09840.23173.2421-0.0334.46650.16620.0048-1.28450.217-0.2123-0.31290.8957-0.13090.02250.9745-0.08330.07231.10130.09811.5075-44.0544-34.304113.6519
42.4654-0.1648-0.47033.09080.22732.64470.16280.5496-0.8609-0.1746-0.22770.2810.3209-0.70320.0650.7524-0.09680.00081.1783-0.1611.0563-60.5277-19.585810.5798
59.56160.41371.96522.66250.610.46330.5005-0.29650.6831-0.2364-0.52210.42740.1177-0.1496-0.05710.6692-0.027-0.00481.25830.17510.696-73.5074-7.410922.0399
67.07910.65070.16890.0538-0.34370.45261.5003-0.3121.21670.4631-1.2449-0.042-0.10880.5288-0.16180.9892-0.13760.18482.3741-0.29721.5774-104.1543-8.271628.0957
75.73440.54540.83832.9403-0.15911.12330.6643-0.19350.68260.1491-0.486-0.75010.11040.1878-0.1750.8136-0.1595-0.10511.07790.14451.0646-38.6716-7.797429.3436
89.1876-1.15815.10820.2205-0.27121.63480.6161-0.7757-0.2854-0.0323-0.46350.54730.3552-0.5153-0.05370.9322-0.12960.02571.8095-0.10671.3276-89.6131-12.565723.3535
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 0 through 160 )A0 - 160
2X-RAY DIFFRACTION2chain 'A' and (resid 161 through 230 )A161 - 230
3X-RAY DIFFRACTION3chain 'A' and (resid 231 through 284 )A231 - 284
4X-RAY DIFFRACTION4chain 'A' and (resid 285 through 407 )A285 - 407
5X-RAY DIFFRACTION5chain 'A' and (resid 408 through 479 )A408 - 479
6X-RAY DIFFRACTION6chain 'A' and (resid 480 through 526 )A480 - 526
7X-RAY DIFFRACTION7chain 'A' and (resid 527 through 604 )A527 - 604
8X-RAY DIFFRACTION8chain 'A' and (resid 605 through 657 )A605 - 657

+
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