[English] 日本語
Yorodumi
- PDB-6qxu: Human TNKS1 in complex with 6,8-Difluoro-2-[4-(1-hydroxy-1-methyl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6qxu
TitleHuman TNKS1 in complex with 6,8-Difluoro-2-[4-(1-hydroxy-1-methyl-ethyl)-phenyl]-3H-quinazolin-4-one
ComponentsPoly [ADP-ribose] polymerase tankyrase-1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / TANKYRASE / PARP / INHIBITOR / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX / TRANSFERASE
Function / homology
Function and homology information


negative regulation of telomeric DNA binding / negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric / regulation of telomere maintenance via telomerase / 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 ...negative regulation of telomeric DNA binding / negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric / regulation of telomere maintenance via telomerase / 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 / mitotic spindle pole / NAD+-protein ADP-ribosyltransferase activity / positive regulation of telomere capping / NAD+ ADP-ribosyltransferase activity / Transferases; Glycosyltransferases; Pentosyltransferases / mRNA transport / spindle assembly / nuclear pore / positive regulation of telomerase activity / positive regulation of telomere maintenance via telomerase / nucleotidyltransferase activity / mitotic spindle organization / TCF dependent signaling in response to WNT / Degradation of AXIN / peptidyl-threonine phosphorylation / Wnt signaling pathway / protein polyubiquitination / Regulation of PTEN stability and activity / positive regulation of canonical Wnt signaling pathway / protein transport / histone binding / peptidyl-serine phosphorylation / nuclear membrane / chromosome, telomeric region / nuclear body / Ub-specific processing proteases / cell division / Golgi membrane / Golgi apparatus / positive regulation of transcription by RNA polymerase II / zinc ion binding / nucleoplasm / nucleus / cytosol / cytoplasm
Similarity search - Function
Phosphoenolpyruvate Carboxykinase; domain 3 - #10 / Phosphoenolpyruvate Carboxykinase; domain 3 / Ankyrin repeats (many copies) / 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 ...Phosphoenolpyruvate Carboxykinase; domain 3 - #10 / Phosphoenolpyruvate Carboxykinase; domain 3 / Ankyrin repeats (many copies) / 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 / Alpha-Beta Complex / Alpha Beta
Similarity search - Domain/homology
BETA-MERCAPTOETHANOL / Chem-JKN / Poly [ADP-ribose] polymerase tankyrase-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.2 Å
AuthorsMusil, D. / Lehmann, D. / Buchstaller, H.-P.
CitationJournal: J.Med.Chem. / Year: 2019
Title: Discovery and Optimization of 2-Arylquinazolin-4-ones into a Potent and Selective Tankyrase Inhibitor Modulating Wnt Pathway Activity.
Authors: Buchstaller, H.P. / Anlauf, U. / Dorsch, D. / Kuhn, D. / Lehmann, M. / Leuthner, B. / Musil, D. / Radtki, D. / Ritzert, C. / Rohdich, F. / Schneider, R. / Esdar, C.
History
DepositionMar 8, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 14, 2019Provider: repository / Type: Initial release
Revision 1.1Sep 25, 2019Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Poly [ADP-ribose] polymerase tankyrase-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)24,6724
Polymers24,2121
Non-polymers4603
Water6,035335
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area200 Å2
ΔGint-2 kcal/mol
Surface area10570 Å2
MethodPISA
Unit cell
Length a, b, c (Å)77.940, 94.640, 62.340
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221

-
Components

#1: Protein Poly [ADP-ribose] polymerase tankyrase-1 / ADP-ribosyltransferase diphtheria toxin-like 5 / ARTD5 / Poly [ADP-ribose] polymerase 5A / Protein ...ADP-ribosyltransferase diphtheria toxin-like 5 / ARTD5 / Poly [ADP-ribose] polymerase 5A / Protein poly-ADP-ribosyltransferase tankyrase-1 / TNKS-1 / TRF1-interacting ankyrin-related ADP-ribose polymerase / Tankyrase I / Tankyrase-1 / TANK1


Mass: 24212.451 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TNKS, PARP5A, PARPL, TIN1, TINF1, TNKS1 / Production host: Escherichia coli (E. coli)
References: UniProt: O95271, NAD+ ADP-ribosyltransferase, Transferases; Glycosyltransferases; Pentosyltransferases
#2: Chemical ChemComp-BME / BETA-MERCAPTOETHANOL / 2-Mercaptoethanol


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS
#3: Chemical ChemComp-JKN / 6,8-bis(fluoranyl)-2-[4-(2-oxidanylpropan-2-yl)phenyl]-3~{H}-quinazolin-4-one


Mass: 316.302 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H14F2N2O2
#4: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 335 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.37 Å3/Da / Density % sol: 48.19 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 1.0 M Ammonium Sulfate, 0.1 M HEPES pH 7.0, 0.5% w/v PEG 8000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.999881 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Feb 2, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.999881 Å / Relative weight: 1
ReflectionResolution: 1.2→43.29 Å / Num. all: 438187 / Num. obs: 70543 / % possible obs: 96.6 % / Redundancy: 6.2 % / Biso Wilson estimate: 16.85 Å2 / CC1/2: 0.999 / Rrim(I) all: 0.053 / Net I/σ(I): 14.8
Reflection shellResolution: 1.2→1.27 Å / Redundancy: 5.1 % / Mean I/σ(I) obs: 1.2 / Num. unique all: 56203 / Num. unique obs: 11113 / CC1/2: 0.713 / Rrim(I) all: 1.255 / % possible all: 95

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: In-house structure

Resolution: 1.2→13.79 Å / Cor.coef. Fo:Fc: 0.97 / Cor.coef. Fo:Fc free: 0.964 / SU R Cruickshank DPI: 0.043 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.047 / SU Rfree Blow DPI: 0.049 / SU Rfree Cruickshank DPI: 0.045
RfactorNum. reflection% reflectionSelection details
Rfree0.213 3521 5 %RANDOM
Rwork0.189 ---
obs0.19 70484 96.8 %-
Displacement parametersBiso mean: 22.59 Å2
Baniso -1Baniso -2Baniso -3
1-1.4763 Å20 Å20 Å2
2---1.6661 Å20 Å2
3---0.1898 Å2
Refine analyzeLuzzati coordinate error obs: 0.2 Å
Refinement stepCycle: 1 / Resolution: 1.2→13.79 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1682 0 28 336 2046
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.011874HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.072531HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d672SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes331HARMONIC5
X-RAY DIFFRACTIONt_it1874HARMONIC20
X-RAY DIFFRACTIONt_nbd0SEMIHARMONIC5
X-RAY DIFFRACTIONt_omega_torsion4.55
X-RAY DIFFRACTIONt_other_torsion15.34
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion226SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact2413SEMIHARMONIC4
LS refinement shellResolution: 1.2→1.21 Å / Total num. of bins used: 50
RfactorNum. reflection% reflection
Rfree0.4261 -4.96 %
Rwork0.4852 1340 -
all0.4819 1410 -
obs--77.74 %
Refinement TLS params.Method: refined / Origin x: -21.2017 Å / Origin y: -18.6126 Å / Origin z: 4.035 Å
111213212223313233
T-0.0537 Å2-0.0024 Å20.0009 Å2--0.0225 Å20.0031 Å2--0.0034 Å2
L0.5464 °20.0364 °2-0.1814 °2-0.8818 °20.0248 °2--0.4038 °2
S0.0052 Å °-0.002 Å °-0.0298 Å °0.0573 Å °-0.0321 Å °-0.0577 Å °0.0023 Å °-0.0057 Å °0.0269 Å °
Refinement TLS groupSelection details: { A|* }

+
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