[English] 日本語
Yorodumi
- PDB-6boe: TBK1 in complex with amide-coupled tetrazole analog of amlexanox -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6boe
TitleTBK1 in complex with amide-coupled tetrazole 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 / positive regulation of TORC2 signaling / dendritic cell proliferation / regulation of type I interferon production / T follicular helper cell differentiation / serine/threonine protein kinase complex / positive regulation of type I interferon-mediated signaling pathway / Interleukin-37 signaling ...IRF3 mediated activation of type 1 IFN / STAT6-mediated induction of chemokines / positive regulation of xenophagy / positive regulation of TORC2 signaling / dendritic cell proliferation / regulation of type I interferon production / T follicular helper cell differentiation / serine/threonine protein kinase complex / positive regulation of type I interferon-mediated signaling pathway / Interleukin-37 signaling / IRF3-mediated induction of type I IFN / cGAS/STING signaling pathway / TNFR1-induced proapoptotic signaling / TRAF6 mediated IRF7 activation / toll-like receptor 4 signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / type I interferon-mediated signaling pathway / positive regulation of interferon-alpha production / positive regulation of macroautophagy / peptidyl-threonine phosphorylation / positive regulation of type I interferon production / canonical NF-kappaB signal transduction / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / TICAM1-dependent activation of IRF3/IRF7 / Regulation of innate immune responses to cytosolic DNA / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / negative regulation of TORC1 signaling / PINK1-PRKN Mediated Mitophagy / antiviral innate immune response / positive regulation of TORC1 signaling / positive regulation of autophagy / activation of innate immune response / positive regulation of interferon-beta production / Negative regulators of DDX58/IFIH1 signaling / Regulation of TNFR1 signaling / DDX58/IFIH1-mediated induction of interferon-alpha/beta / macroautophagy / phosphoprotein binding / peptidyl-serine phosphorylation / response to virus / SARS-CoV-1 activates/modulates innate immune responses / TRAF3-dependent IRF activation pathway / protein phosphatase binding / defense response to virus / Potential therapeutics for SARS / nucleic acid binding / RNA polymerase II-specific DNA-binding transcription factor binding / protein phosphorylation / positive regulation of canonical NF-kappaB signal transduction / non-specific serine/threonine protein kinase / protein kinase activity / defense response to Gram-positive bacterium / inflammatory response / negative regulation of gene expression / innate immune response / protein serine kinase activity / intracellular membrane-bounded organelle / 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) / Phosphorylase Kinase; 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) / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); 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-E0S / Serine/threonine-protein kinase TBK1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 3.598 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)76,3912
Polymers76,0261
Non-polymers3651
Water00
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 area31970 Å2
Unit cell
Length a, b, c (Å)134.483, 134.483, 85.499
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-E0S / 2-amino-5-oxo-7-(propan-2-yl)-N-(1H-tetrazol-5-yl)-5H-[1]benzopyrano[2,3-b]pyridine-3-carboxamide


Mass: 365.346 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H15N7O3

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.93 Å3/Da / Density % sol: 57.96 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 0.1 M HEPES pH 7.5, 5% PEG 8000 / PH range: 7.0-8.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 1.03312 Å
DetectorType: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Apr 12, 2017
RadiationMonochromator: Double Crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.03312 Å / Relative weight: 1
ReflectionResolution: 3.6→35.349 Å / Num. obs: 10637 / % possible obs: 99.9 % / Redundancy: 18.985 % / Biso Wilson estimate: 166.12 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.141 / Rrim(I) all: 0.145 / Χ2: 0.967 / Net I/σ(I): 16.36 / Num. measured all: 201948
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
3.6-3.8220.0011.5791.5534062171117030.6681.6299.5
3.82-4.0819.1210.9163.0630460159415930.8870.94199.9
4.08-4.418.7860.4696.5227390145914580.9740.48399.9
4.4-4.8220.0560.27212.0527858138913890.9930.279100
4.82-5.3819.6360.20616.3724290123712370.9950.211100
5.38-6.2119.0590.18617.2920965110011000.9950.191100
6.21-7.5817.4840.10628.7166279519510.9990.11100
7.58-10.6316.9850.06157.181277375275210.063100
10.63-35.34916.570.05567.59752345945410.05798.9

-
Phasing

PhasingMethod: molecular replacement
Phasing MR
Highest resolutionLowest resolution
Rotation6.84 Å48.13 Å
Translation6.84 Å48.13 Å

-
Processing

Software
NameVersionClassification
PHENIX1.11.1_2575refinement
XSCALE0.5.32data scaling
PHASER2.7.16phasing
PDB_EXTRACT3.22data extraction
Cootmodel building
XDSdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4IM0

4im0


Resolution: 3.598→35.349 Å / SU ML: 0.59 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 34.16 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2911 1064 9.85 %
Rwork0.2414 18025 -
obs0.2465 10591 99.52 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 293.14 Å2 / Biso mean: 182.1693 Å2 / Biso min: 113.93 Å2
Refinement stepCycle: final / Resolution: 3.598→35.349 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4868 0 27 0 4895
Biso mean--187.27 --
Num. residues----600
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0014997
X-RAY DIFFRACTIONf_angle_d0.3956745
X-RAY DIFFRACTIONf_chiral_restr0.037747
X-RAY DIFFRACTIONf_plane_restr0.003855
X-RAY DIFFRACTIONf_dihedral_angle_d6.2483008
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 14

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
3.5982-3.68810.45251400.42771286142698
3.6881-3.78770.38031420.364812831425100
3.7877-3.8990.38421510.320312861437100
3.899-4.02470.35961370.317112971434100
4.0247-4.16830.34611290.298512791408100
4.1683-4.33490.31791420.247413191461100
4.3349-4.53180.28591440.244812871431100
4.5318-4.77020.29561400.239912901430100
4.7702-5.06830.26961400.231312821422100
5.0683-5.45830.29661440.259212871431100
5.4583-6.00520.40011420.294212951437100
6.0052-6.86860.35141360.293413051441100
6.8686-8.63280.29161320.232612881420100
8.6328-35.35030.19991500.16041241139196
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)
19.1575-7.2281-5.58578.8775.24456.0375-0.43230.81921.44770.80670.9133-1.2941.6419-0.2351-0.54772.1334-0.1407-0.18091.76880.33831.6915-0.2388-21.8694-21.2621
24.5729-1.5725-1.95529.5417-4.52769.6639-0.13940.74720.7105-0.794-0.5544-0.5739-0.20780.57010.70931.2226-0.3581-0.07431.60840.07141.1633-2.8901-36.5681-16.974
30.30770.37840.44486.05820.43858.8112-0.13680.9870.4513-0.2-0.3028-0.95290.17610.67060.67561.9264-0.2607-0.21011.59730.27811.4332-1.9529-39.4561-15.8047
42.32930.02291.29247.4714-2.2989.4732-0.7038-0.00890.5522-0.0633-0.0957-1.8786-0.45652.51470.69841.7503-0.0031-0.15192.08860.30642.085412.2067-48.4426-3.9668
55.78821.4631-1.24171.530.45941.584-0.61630.964-1.2395-0.37540.4235-0.66330.8759-0.27220.26782.0954-0.16540.14581.3875-0.07241.3719-8.8434-62.884-6.1463
62.532.715-2.41958.558-0.66942.4832-0.650.3521-0.4515-0.86240.2925-1.57740.81720.00930.30981.6528-0.0059-0.13661.29970.06091.2066-11.6544-54.0998.1502
73.9654.15071.37167.92613.56061.13220.7542-0.375-0.27841.8084-1.01550.78680.6875-0.15090.2112.0183-0.2996-0.2741.26830.14351.62-36.1223-77.56299.493
84.90124.73810.01097.21651.45382.30450.3824-0.2240.10060.9484-0.1076-0.1501-0.1686-0.2738-0.20911.7578-0.0664-0.3161.42560.07881.3177-13.0995-37.955115.1083
95.63073.23993.29723.39393.7577-0.26160.1416-0.3983-0.84130.8696-0.2869-0.01130.4653-0.26740.2482.7181-0.61010.18441.77940.11611.1963-33.6654-83.77079.1557
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 0 through 60 )A0 - 60
2X-RAY DIFFRACTION2chain 'A' and (resid 61 through 129 )A61 - 129
3X-RAY DIFFRACTION3chain 'A' and (resid 130 through 176 )A130 - 176
4X-RAY DIFFRACTION4chain 'A' and (resid 177 through 246 )A177 - 246
5X-RAY DIFFRACTION5chain 'A' and (resid 247 through 369 )A247 - 369
6X-RAY DIFFRACTION6chain 'A' and (resid 370 through 409 )A370 - 409
7X-RAY DIFFRACTION7chain 'A' and (resid 410 through 525 )A410 - 525
8X-RAY DIFFRACTION8chain 'A' and (resid 526 through 604 )A526 - 604
9X-RAY DIFFRACTION9chain '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