[English] 日本語
Yorodumi
- PDB-8s60: Tankyrase 2 in complex with a quinazolin-4-one inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8s60
TitleTankyrase 2 in complex with a quinazolin-4-one inhibitor
Components(Poly [ADP-ribose] polymerase tankyrase- ...) x 2
KeywordsTRANSFERASE / Inhibitor / quinazolin-4-one / Tankyrase 2
Function / homology
Function and homology information


XAV939 stabilizes AXIN / positive regulation of telomere capping / NAD+ ADP-ribosyltransferase / negative regulation of telomere maintenance via telomere lengthening / protein auto-ADP-ribosylation / protein localization to chromosome, telomeric region / NAD+-protein-aspartate ADP-ribosyltransferase activity / protein poly-ADP-ribosylation / NAD+-protein-glutamate ADP-ribosyltransferase activity / NAD+-protein mono-ADP-ribosyltransferase activity ...XAV939 stabilizes AXIN / positive regulation of telomere capping / NAD+ ADP-ribosyltransferase / negative regulation of telomere maintenance via telomere lengthening / protein auto-ADP-ribosylation / protein localization to chromosome, telomeric region / NAD+-protein-aspartate ADP-ribosyltransferase activity / protein poly-ADP-ribosylation / NAD+-protein-glutamate ADP-ribosyltransferase activity / NAD+-protein mono-ADP-ribosyltransferase activity / pericentriolar material / Transferases; Glycosyltransferases; Pentosyltransferases / NAD+ poly-ADP-ribosyltransferase activity / positive regulation of telomere maintenance via telomerase / nucleotidyltransferase activity / TCF dependent signaling in response to WNT / Degradation of AXIN / Regulation of PTEN stability and activity / Wnt signaling pathway / protein polyubiquitination / positive regulation of canonical Wnt signaling pathway / nuclear envelope / chromosome, telomeric region / Ub-specific processing proteases / Golgi membrane / perinuclear region of cytoplasm / enzyme binding / metal ion binding / nucleus / cytoplasm / cytosol
Similarity search - Function
Ankyrin repeat / Poly(ADP-ribose) polymerase catalytic domain / Poly(ADP-ribose) polymerase, catalytic domain / PARP catalytic domain profile. / SAM domain (Sterile alpha motif) / SAM domain profile. / Sterile alpha motif. / Sterile alpha motif domain / Sterile alpha motif/pointed domain superfamily / Ankyrin repeat ...Ankyrin repeat / Poly(ADP-ribose) polymerase catalytic domain / Poly(ADP-ribose) polymerase, catalytic domain / PARP catalytic domain profile. / SAM domain (Sterile alpha motif) / SAM domain profile. / Sterile alpha motif. / Sterile alpha motif domain / Sterile alpha motif/pointed domain superfamily / Ankyrin repeat / Ankyrin repeats (3 copies) / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily
Similarity search - Domain/homology
: / Poly [ADP-ribose] polymerase tankyrase-2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.801 Å
AuthorsBosetti, C. / Paakkonen, J. / Lehtio, L.
Funding support Finland, 1items
OrganizationGrant numberCountry
Jane and Aatos Erkko Foundation Finland
CitationJournal: Eur.J.Med.Chem. / Year: 2025
Title: Substitutions at the C-8 position of quinazolin-4-ones improve the potency of nicotinamide site binding tankyrase inhibitors.
Authors: Bosetti, C. / Kampasis, D. / Brinch, S.A. / Galera-Prat, A. / Karelou, M. / Dhakar, S.S. / Alaviuhkola, J. / Waaler, J. / Lehtio, L. / Kostakis, I.K.
History
DepositionFeb 26, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 12, 2025Provider: repository / Type: Initial release
Revision 1.1Mar 26, 2025Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Poly [ADP-ribose] polymerase tankyrase-2
B: Poly [ADP-ribose] polymerase tankyrase-2
C: Poly [ADP-ribose] polymerase tankyrase-2
D: Poly [ADP-ribose] polymerase tankyrase-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)50,97013
Polymers49,6924
Non-polymers1,2789
Water3,135174
1
A: Poly [ADP-ribose] polymerase tankyrase-2
B: Poly [ADP-ribose] polymerase tankyrase-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)25,5317
Polymers24,8462
Non-polymers6855
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
C: Poly [ADP-ribose] polymerase tankyrase-2
D: Poly [ADP-ribose] polymerase tankyrase-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)25,4396
Polymers24,8462
Non-polymers5934
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)90.419, 98.162, 119.579
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number20
Space group name H-MC2221
Components on special symmetry positions
IDModelComponents
11A-1326-

HOH

21C-1324-

HOH

-
Components

-
Poly [ADP-ribose] polymerase tankyrase- ... , 2 types, 4 molecules ACBD

#1: Protein Poly [ADP-ribose] polymerase tankyrase-2 / ADP-ribosyltransferase diphtheria toxin-like 6 / ARTD6 / Poly [ADP-ribose] polymerase 5B / Protein ...ADP-ribosyltransferase diphtheria toxin-like 6 / ARTD6 / Poly [ADP-ribose] polymerase 5B / Protein poly-ADP-ribosyltransferase tankyrase-2 / TNKS-2 / TRF1-interacting ankyrin-related ADP-ribose polymerase 2 / Tankyrase II / Tankyrase-2 / TANK2 / Tankyrase-like protein / Tankyrase-related protein


Mass: 19482.053 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Details: Chymotrypsin was included in the crystallization mixture. Consequently, there aren't missing residues, but a cut in the protein chain.
Source: (gene. exp.) Homo sapiens (human) / Gene: TNKS2, PARP5B, TANK2, TNKL / Production host: Escherichia coli (E. coli)
References: UniProt: Q9H2K2, NAD+ ADP-ribosyltransferase, Transferases; Glycosyltransferases; Pentosyltransferases
#2: Protein/peptide Poly [ADP-ribose] polymerase tankyrase-2 / ADP-ribosyltransferase diphtheria toxin-like 6 / ARTD6 / Poly [ADP-ribose] polymerase 5B / Protein ...ADP-ribosyltransferase diphtheria toxin-like 6 / ARTD6 / Poly [ADP-ribose] polymerase 5B / Protein poly-ADP-ribosyltransferase tankyrase-2 / TNKS-2 / TRF1-interacting ankyrin-related ADP-ribose polymerase 2 / Tankyrase II / Tankyrase-2 / TANK2 / Tankyrase-like protein / Tankyrase-related protein


Mass: 5364.037 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Details: Chymotrypsin was included in the crystallization mixture. Consequently, there aren't missing residues, but a cut in the protein chain.
Source: (gene. exp.) Homo sapiens (human) / Gene: TNKS2, PARP5B, TANK2, TNKL / Production host: Escherichia coli (E. coli)
References: UniProt: Q9H2K2, NAD+ ADP-ribosyltransferase, Transferases; Glycosyltransferases; Pentosyltransferases

-
Non-polymers , 5 types, 183 molecules

#3: Chemical ChemComp-A1H5B / 8-nitro-2-[4-(trifluoromethyl)phenyl]-3H-quinazolin-4-one


Mass: 335.238 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C15H8F3N3O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#5: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: SO4
#6: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 174 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.67 Å3/Da / Density % sol: 53.96 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: 100 mM Tris pH 8.5, 22% PEG3350, 200 mM Li2SO4, 250 mM NaCl, 20% glycerol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: MAX IV / Beamline: BioMAX / Wavelength: 0.920013 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: May 1, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.920013 Å / Relative weight: 1
ReflectionResolution: 1.8→50 Å / Num. obs: 49407 / % possible obs: 100 % / Redundancy: 13.54 % / CC1/2: 0.999 / Rmerge(I) obs: 0.079 / Rrim(I) all: 0.082 / Net I/σ(I): 17.75
Reflection shellResolution: 1.8→1.91 Å / Redundancy: 13.88 % / Rmerge(I) obs: 0.991 / Mean I/σ(I) obs: 2.11 / Num. unique obs: 7875 / CC1/2: 0.876 / Rrim(I) all: 1.029 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.801→42.324 Å / Cor.coef. Fo:Fc: 0.968 / Cor.coef. Fo:Fc free: 0.957 / SU B: 2.5 / SU ML: 0.076 / Cross valid method: FREE R-VALUE / ESU R: 0.11 / ESU R Free: 0.109
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2147 2471 5.001 %
Rwork0.1808 46935 -
all0.183 --
obs-49406 99.953 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 36.444 Å2
Baniso -1Baniso -2Baniso -3
1--0.394 Å2-0 Å20 Å2
2---1.605 Å2-0 Å2
3---1.999 Å2
Refinement stepCycle: LAST / Resolution: 1.801→42.324 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3341 0 76 174 3591
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0133512
X-RAY DIFFRACTIONr_bond_other_d0.0010.0153146
X-RAY DIFFRACTIONr_angle_refined_deg1.4021.6414739
X-RAY DIFFRACTIONr_angle_other_deg1.3011.587233
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.6925417
X-RAY DIFFRACTIONr_dihedral_angle_2_deg29.9521.196209
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.04215574
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.7841528
X-RAY DIFFRACTIONr_chiral_restr0.0670.2421
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.024019
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02891
X-RAY DIFFRACTIONr_nbd_refined0.1930.2567
X-RAY DIFFRACTIONr_symmetry_nbd_other0.1740.22842
X-RAY DIFFRACTIONr_nbtor_refined0.1640.21662
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0710.21620
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1250.2164
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1710.28
X-RAY DIFFRACTIONr_nbd_other0.1790.234
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.1690.214
X-RAY DIFFRACTIONr_mcbond_it2.6393.6241668
X-RAY DIFFRACTIONr_mcbond_other2.6373.6221667
X-RAY DIFFRACTIONr_mcangle_it3.7725.4092079
X-RAY DIFFRACTIONr_mcangle_other3.7715.4112080
X-RAY DIFFRACTIONr_scbond_it3.3774.0251843
X-RAY DIFFRACTIONr_scbond_other3.3544.0131828
X-RAY DIFFRACTIONr_scangle_it5.2355.8832658
X-RAY DIFFRACTIONr_scangle_other5.2095.8632635
X-RAY DIFFRACTIONr_lrange_it6.98441.1243827
X-RAY DIFFRACTIONr_lrange_other6.9841.0113808
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.801-1.8480.2931810.2633434X-RAY DIFFRACTION99.8895
1.848-1.8990.2561750.2423326X-RAY DIFFRACTION100
1.899-1.9540.2441720.2213260X-RAY DIFFRACTION100
1.954-2.0140.2341670.2013180X-RAY DIFFRACTION100
2.014-2.080.2391620.1893071X-RAY DIFFRACTION100
2.08-2.1530.221560.1792972X-RAY DIFFRACTION99.968
2.153-2.2340.2261510.1832873X-RAY DIFFRACTION100
2.234-2.3250.1951460.1682769X-RAY DIFFRACTION100
2.325-2.4280.2251390.1752635X-RAY DIFFRACTION100
2.428-2.5470.2181340.1852544X-RAY DIFFRACTION99.9627
2.547-2.6850.2161280.1982437X-RAY DIFFRACTION100
2.685-2.8470.2151200.1872292X-RAY DIFFRACTION100
2.847-3.0440.2231150.1842181X-RAY DIFFRACTION100
3.044-3.2880.2281060.1952013X-RAY DIFFRACTION100
3.288-3.6010.221990.1841871X-RAY DIFFRACTION100
3.601-4.0260.219880.1681682X-RAY DIFFRACTION100
4.026-4.6480.178800.1451507X-RAY DIFFRACTION100
4.648-5.690.156680.1521298X-RAY DIFFRACTION100
5.69-8.0380.256530.1941013X-RAY DIFFRACTION100
8.038-42.3240.222310.195578X-RAY DIFFRACTION97.2843

+
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