[English] 日本語
Yorodumi
- PDB-6cq4: TBK1 in Complex with Cyclohexyl Analog of Amlexanox -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6cq4
TitleTBK1 in Complex with Cyclohexyl Analog of Amlexanox
ComponentsSerine/threonine-protein kinase TBK1
KeywordsTRANSFERASE / TBK1 / kinase / amlexanox
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 / dendritic cell proliferation / regulation of type I interferon production / IRF3-mediated induction of type I IFN / positive regulation of type I interferon-mediated signaling pathway / Interleukin-37 signaling / cGAS/STING signaling pathway ...IRF3 mediated activation of type 1 IFN / STAT6-mediated induction of chemokines / positive regulation of xenophagy / serine/threonine protein kinase complex / dendritic cell proliferation / regulation of type I interferon production / IRF3-mediated induction of type I IFN / positive regulation of type I interferon-mediated signaling pathway / Interleukin-37 signaling / cGAS/STING signaling pathway / TNFR1-induced proapoptotic signaling / toll-like receptor 4 signaling pathway / TRAF6 mediated IRF7 activation / cytoplasmic pattern recognition receptor signaling pathway / type I interferon-mediated signaling pathway / antiviral innate immune response / positive regulation of macroautophagy / positive regulation of type I interferon production / canonical NF-kappaB signal transduction / positive regulation of interferon-alpha production / positive regulation of autophagy / negative regulation of TORC1 signaling / positive regulation of TORC1 signaling / TICAM1-dependent activation of IRF3/IRF7 / activation of innate immune response / Regulation of innate immune responses to cytosolic DNA / positive regulation of interferon-beta production / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Negative regulators of DDX58/IFIH1 signaling / phosphoprotein binding / Regulation of TNFR1 signaling / peptidyl-threonine phosphorylation / DDX58/IFIH1-mediated induction of interferon-alpha/beta / response to virus / 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 / intracellular membrane-bounded organelle / innate immune response / protein serine kinase activity / 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 / cytoplasm / cytosol
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-F8P / Serine/threonine-protein kinase TBK1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.2 Å
AuthorsBeyett, T.S. / Tesmer, J.J.G.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)DK100319 United States
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)DK060591 United States
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)DK60597 United States
CitationJournal: Bioorg. Med. Chem. / Year: 2018
Title: Design, synthesis, and biological activity of substituted 2-amino-5-oxo-5H-chromeno[2,3-b]pyridine-3-carboxylic acid derivatives as inhibitors of the inflammatory kinases TBK1 and IKK epsilon ...Title: Design, synthesis, and biological activity of substituted 2-amino-5-oxo-5H-chromeno[2,3-b]pyridine-3-carboxylic acid derivatives as inhibitors of the inflammatory kinases TBK1 and IKK epsilon for the treatment of obesity.
Authors: Beyett, T.S. / Gan, X. / Reilly, S.M. / Gomez, A.V. / Chang, L. / Tesmer, J.J.G. / Saltiel, A.R. / Showalter, H.D.
History
DepositionMar 14, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 5, 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)76,4002
Polymers76,0261
Non-polymers3741
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area31930 Å2
MethodPISA
Unit cell
Length a, b, c (Å)134.604, 134.604, 84.505
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 / Production host: Spodoptera frugiperda (fall armyworm) / Strain (production host): SF9
References: UniProt: Q9UHD2, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-F8P / 2-amino-7-(4,4-difluorocyclohexyl)-5-oxo-5H-[1]benzopyrano[2,3-b]pyridine-3-carboxylic acid / 7-(4,4-difluorocyclohexyl) Analog of Amlexanox


Mass: 374.338 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H16F2N2O4 / Feature type: SUBJECT OF INVESTIGATION

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.91 Å3/Da / Density % sol: 57.69 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 0.1 M HEPES pH 7.5, 4% PEG 8000, 10% DMSO

-
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: Aug 16, 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: 3.2→47.98 Å / Num. obs: 14851 / % possible obs: 99.8 % / Redundancy: 20.243 % / Biso Wilson estimate: 117.59 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.121 / Rrim(I) all: 0.124 / Χ2: 1.057 / Net I/σ(I): 16.59 / Num. measured all: 300633
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsCC1/2Rrim(I) all% possible all
3.2-3.3920.7331.4282.2923400.8231.46498.9
3.39-3.6320.4640.84.222280.9320.821100
3.63-3.9118.2470.3717.920630.9850.38199.9
3.91-4.2921.7110.20414.5619320.9960.208100
4.29-4.7921.3910.12921.9617430.9980.132100
4.79-5.5221.0320.10926.0715460.9980.112100
5.52-6.7419.8470.10627.1213240.9980.109100
6.74-9.4318.4290.06639.9310470.9990.06899.9
9.43-47.9818.4110.05949.226280.9980.06198.7

-
Processing

Software
NameVersionClassification
PHENIX1.11.1_2575refinement
XSCALEdata scaling
PDB_EXTRACT3.24data extraction
XDSdata reduction
PHASERphasing
Cootmodel building
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4IM0

4im0


Resolution: 3.2→47.98 Å / SU ML: 0.66 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 33.26
RfactorNum. reflection% reflection
Rfree0.2723 738 4.96 %
Rwork0.233 --
obs0.235 14823 99.6 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 316.89 Å2 / Biso mean: 149.3185 Å2 / Biso min: 49.75 Å2
Refinement stepCycle: final / Resolution: 3.2→47.98 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4883 0 27 0 4910
Biso mean--103.03 --
Num. residues----604
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0025013
X-RAY DIFFRACTIONf_angle_d0.3896773
X-RAY DIFFRACTIONf_chiral_restr0.037751
X-RAY DIFFRACTIONf_plane_restr0.003860
X-RAY DIFFRACTIONf_dihedral_angle_d13.0293019
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 10

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
3.2-3.31440.45121360.38672657279398
3.3144-3.4470.43541390.361426752814100
3.447-3.60390.36761460.325726582804100
3.6039-3.79380.31981500.295826942844100
3.7938-4.03140.30231420.263926602802100
4.0314-4.34250.29591380.23826942832100
4.3425-4.77910.19831340.213726952829100
4.7791-5.46980.24811400.222426992839100
5.4698-6.88810.34761360.254226842820100
6.8881-47.9850.20841350.17092648278398
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)
14.87284.3147-2.39637.58981.26156.53770.3642-0.1673-0.23170.3641-0.0938-1.47170.93030.0671-0.33281.02180.0467-0.03411.60050.08731.4473115.6092-11.776-6.7213
25.21270.6467-2.2592.9681-0.32123.5686-0.14410.5402-0.5195-0.3587-0.1138-0.45830.1701-0.17070.31350.80880.1366-0.01611.32460.03311.2792101.2005-16.7455-2.6572
30.09730.43920.11944.3905-2.90736.40590.13210.0387-0.7507-0.0202-0.3999-0.63741.3459-0.00130.42631.091-0.15110.01461.30930.10171.728294.7562-30.76479.8755
42.7024-0.0730.04241.82310.97631.66520.18760.5585-0.9368-0.0598-0.41440.27810.2432-0.8760.32410.8676-0.1405-0.00461.7992-0.12431.464673.8095-19.679310.4525
54.04212.62312.05021.22590.70620.41120.2206-0.95860.65590.0946-0.28960.19880.1643-0.3221-0.02710.724-0.0925-0.01421.72330.27461.119670.62-7.833126.0638
66.60730.00267.1632-0.60550.59371.76430.1838-1.602-0.4945-0.0341-0.18050.50110.0592-0.7564-0.11120.8624-0.16770.04072.41210.10191.473144.9929-12.751723.2209
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 145 )A61 - 145
3X-RAY DIFFRACTION3chain 'A' and (resid 146 through 284 )A146 - 284
4X-RAY DIFFRACTION4chain 'A' and (resid 285 through 407 )A285 - 407
5X-RAY DIFFRACTION5chain 'A' and (resid 408 through 604 )A408 - 604
6X-RAY DIFFRACTION6chain '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://pdbjlvh1.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