[English] 日本語
Yorodumi
- PDB-6tkm: Tankyrase 2 in complex with an inhibitor (OM-1800) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6tkm
TitleTankyrase 2 in complex with an inhibitor (OM-1800)
ComponentsTankyrase-2
KeywordsTRANSFERASE / Inhibitor / Complex / Poly-ADP-ribosylation / Enzyme
Function / homology
Function and homology information


XAV939 stabilizes AXIN / NAD+ ADP-ribosyltransferase / protein localization to chromosome, telomeric region / negative regulation of telomere maintenance via telomere lengthening / protein auto-ADP-ribosylation / protein poly-ADP-ribosylation / pericentriolar material / NAD+-protein ADP-ribosyltransferase activity / positive regulation of telomere capping / NAD+-protein poly-ADP-ribosyltransferase activity ...XAV939 stabilizes AXIN / NAD+ ADP-ribosyltransferase / protein localization to chromosome, telomeric region / negative regulation of telomere maintenance via telomere lengthening / protein auto-ADP-ribosylation / protein poly-ADP-ribosylation / pericentriolar material / NAD+-protein ADP-ribosyltransferase activity / positive regulation of telomere capping / NAD+-protein poly-ADP-ribosyltransferase activity / Transferases; Glycosyltransferases; Pentosyltransferases / positive regulation of telomere maintenance via telomerase / nucleotidyltransferase activity / TCF dependent signaling in response to WNT / Degradation of AXIN / Wnt signaling pathway / Regulation of PTEN stability and activity / 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 / nucleus / metal ion binding / cytosol / cytoplasm
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 / : / 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
Chem-NG5 / Poly [ADP-ribose] polymerase tankyrase-2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å
AuthorsSowa, S.T. / Lehtio, L.
Funding support Finland, 2items
OrganizationGrant numberCountry
Academy of Finland287063, 294085 Finland
Jane and Aatos Erkko Foundation Finland
CitationJournal: J.Med.Chem. / Year: 2020
Title: Preclinical Lead Optimization of a 1,2,4-Triazole Based Tankyrase Inhibitor.
Authors: Waaler, J. / Leenders, R.G.G. / Sowa, S.T. / Alam Brinch, S. / Lycke, M. / Nieczypor, P. / Aertssen, S. / Murthy, S. / Galera-Prat, A. / Damen, E. / Wegert, A. / Nazare, M. / Lehtio, L. / Krauss, S.
History
DepositionNov 28, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 8, 2020Provider: repository / Type: Initial release
Revision 1.1Jul 22, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Jan 24, 2024Group: 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
AAA: Tankyrase-2
BBB: Tankyrase-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,7496
Polymers54,6002
Non-polymers1,1504
Water55831
1
AAA: Tankyrase-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)27,8753
Polymers27,3001
Non-polymers5752
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
BBB: Tankyrase-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)27,8753
Polymers27,3001
Non-polymers5752
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)42.320, 77.410, 148.680
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Noncrystallographic symmetry (NCS)NCS domain: (Details: Chains A B)

-
Components

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


Mass: 27299.764 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
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: Chemical ChemComp-NG5 / ~{N}-[3-[5-(5-ethoxypyridin-2-yl)-4-(2-fluorophenyl)-1,2,4-triazol-3-yl]cyclobutyl]-1,5-naphthyridine-4-carboxamide


Mass: 509.534 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C28H24FN7O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 31 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.6 Å3/Da / Density % sol: 52.65 %
Crystal growTemperature: 295.15 K / Method: vapor diffusion, sitting drop / Details: 7.5-25% PEG 6000, Bicine, pH = 9.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Jul 1, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.7→50 Å / Num. obs: 25517 / % possible obs: 98.4 % / Redundancy: 3.4339 % / CC1/2: 0.974 / Net I/σ(I): 5.09
Reflection shellResolution: 2.7→2.77 Å / Mean I/σ(I) obs: 1.21 / Num. unique obs: 1935 / CC1/2: 0.627

-
Processing

Software
NameVersionClassification
REFMAC5.8.0257refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5NOB

5nob


Resolution: 2.7→29.735 Å / Cor.coef. Fo:Fc: 0.913 / Cor.coef. Fo:Fc free: 0.883 / SU B: 18.188 / SU ML: 0.342 / Cross valid method: FREE R-VALUE / ESU R Free: 0.376
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2714 700 5.002 %
Rwork0.237 --
all0.239 --
obs-13994 99.403 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 37.872 Å2
Baniso -1Baniso -2Baniso -3
1-2.141 Å20 Å20 Å2
2--3.474 Å2-0 Å2
3----5.615 Å2
Refinement stepCycle: LAST / Resolution: 2.7→29.735 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3269 0 78 31 3378
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0040.0133440
X-RAY DIFFRACTIONr_bond_other_d0.0020.0182993
X-RAY DIFFRACTIONr_angle_refined_deg1.2751.684642
X-RAY DIFFRACTIONr_angle_other_deg1.1651.66922
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.3225404
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.30921.068206
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.87715542
X-RAY DIFFRACTIONr_dihedral_angle_4_deg13.5641528
X-RAY DIFFRACTIONr_chiral_restr0.040.2414
X-RAY DIFFRACTIONr_chiral_restr_other1.5010.28
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.023912
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02814
X-RAY DIFFRACTIONr_nbd_refined0.1720.2604
X-RAY DIFFRACTIONr_symmetry_nbd_other0.1690.22732
X-RAY DIFFRACTIONr_nbtor_refined0.1620.21597
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0710.21532
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1210.285
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_other0.0380.21
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.1930.27
X-RAY DIFFRACTIONr_nbd_other0.2270.218
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.2160.23
X-RAY DIFFRACTIONr_mcbond_it1.6574.1041631
X-RAY DIFFRACTIONr_mcbond_other1.6574.1031630
X-RAY DIFFRACTIONr_mcangle_it2.9976.142030
X-RAY DIFFRACTIONr_mcangle_other2.9976.1422031
X-RAY DIFFRACTIONr_scbond_it1.2974.151809
X-RAY DIFFRACTIONr_scbond_other1.2974.1491810
X-RAY DIFFRACTIONr_scangle_it2.346.172608
X-RAY DIFFRACTIONr_scangle_other2.346.1692609
X-RAY DIFFRACTIONr_lrange_it4.75145.6093730
X-RAY DIFFRACTIONr_lrange_other4.75145.6023731
X-RAY DIFFRACTIONr_ncsr_local_group_10.1030.056216
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.7-2.770.431510.344972X-RAY DIFFRACTION100
2.77-2.8460.346500.341949X-RAY DIFFRACTION99.8002
2.846-2.9280.341470.307898X-RAY DIFFRACTION99.8943
2.928-3.0180.357480.306904X-RAY DIFFRACTION100
3.018-3.1170.272440.271849X-RAY DIFFRACTION100
3.117-3.2270.263460.264858X-RAY DIFFRACTION100
3.227-3.3490.335420.239795X-RAY DIFFRACTION100
3.349-3.4850.239410.228788X-RAY DIFFRACTION100
3.485-3.640.251390.262745X-RAY DIFFRACTION98.8651
3.64-3.8180.374370.311694X-RAY DIFFRACTION94.0798
3.818-4.0240.254350.232670X-RAY DIFFRACTION99.2958
4.024-4.2680.204350.171658X-RAY DIFFRACTION99.8559
4.268-4.5620.198320.167618X-RAY DIFFRACTION100
4.562-4.9270.2300.16574X-RAY DIFFRACTION100
4.927-5.3970.228290.189543X-RAY DIFFRACTION100
5.397-6.0330.264260.226494X-RAY DIFFRACTION100
6.033-6.9650.258230.202434X-RAY DIFFRACTION99.7817
6.965-8.5250.214200.19379X-RAY DIFFRACTION100
8.525-12.0370.214150.175297X-RAY DIFFRACTION100

+
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