[English] 日本語
Yorodumi
- PDB-4uuh: X-ray crystal structure of human TNKS in complex with a small mol... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4uuh
TitleX-ray crystal structure of human TNKS in complex with a small molecule inhibitor
ComponentsTANKYRASE-1
KeywordsTRANSFERASE / TNKS / INHIBITOR / WNT SIGNALLING
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 / negative regulation of telomere maintenance via telomere lengthening / protein auto-ADP-ribosylation / protein localization to chromosome, telomeric region / 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 / negative regulation of telomere maintenance via telomere lengthening / protein auto-ADP-ribosylation / protein localization to chromosome, telomeric region / protein poly-ADP-ribosylation / pericentriolar material / mitotic spindle pole / NAD+-protein ADP-ribosyltransferase activity / positive regulation of telomere capping / Transferases; Glycosyltransferases; Pentosyltransferases / NAD+ ADP-ribosyltransferase activity / spindle assembly / mRNA transport / 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 / Regulation of PTEN stability and activity / protein polyubiquitination / 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
Chem-T40 / Poly [ADP-ribose] polymerase tankyrase-1
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.52 Å
AuthorsOliver, A.W. / Rajasekaran, M.B. / Pearl, L.H.
CitationJournal: Medchemcommm / Year: 2015
Title: Design and Discovery of 3-Aryl-5-Substituted-Isoquinolin-1- Ones as Potent and Selective Tankyrase Inhibitors
Authors: Elliot, R.J. / Jarvis, A. / Rajasekaran, M.B. / Menon, M. / Bowers, L. / Boffey, R. / Bayford, M. / Firth-Clark, S. / Beevers, R. / Aquil, R. / Kirton, S.B. / Niculescu-Duvaz, D. / Fish, L. ...Authors: Elliot, R.J. / Jarvis, A. / Rajasekaran, M.B. / Menon, M. / Bowers, L. / Boffey, R. / Bayford, M. / Firth-Clark, S. / Beevers, R. / Aquil, R. / Kirton, S.B. / Niculescu-Duvaz, D. / Fish, L. / Lopes, F. / Mcleary, R. / Trindade, I. / Vendrell, E. / Munkonge, F. / Porter, R. / Perrior, T. / Springer, C. / Oliver, A.W. / Pearl, L.H. / Ashworth, A. / Lord, C.J.
History
DepositionJul 28, 2014Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 8, 2015Provider: repository / Type: Initial release
Revision 1.1Jan 13, 2016Group: Database references
Revision 1.2Jan 10, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: TANKYRASE-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)30,43311
Polymers29,4171
Non-polymers1,01510
Water1,820101
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)81.320, 80.890, 83.700
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number24
Space group name H-MI212121
Components on special symmetry positions
IDModelComponents
11A-2321-

GOL

21A-2322-

EDO

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein TANKYRASE-1 / / TANK1 / ADP-RIBOSYLTRANSFERASE DIPHTHERIA TOXIN-LIKE 5 / ARTD 5 / POLY ADP-RIBOSE POLYMERASE 5A / ...TANK1 / ADP-RIBOSYLTRANSFERASE DIPHTHERIA TOXIN-LIKE 5 / ARTD 5 / POLY ADP-RIBOSE POLYMERASE 5A / TNKS-1 / TRF1-INTERACTING ANKYRIN -RELATED ADP-RIBOSE POLYMERASE / TANKYRASE I


Mass: 29417.082 Da / Num. of mol.: 1 / Fragment: CATALYTIC DOMAIN, RESIDUES 1091-1325
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PNIC-BSA4-TNKS1 / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / Variant (production host): ROSETTA2 / References: UniProt: O95271, NAD+ ADP-ribosyltransferase

-
Non-polymers , 5 types, 111 molecules

#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6O2
#5: Chemical ChemComp-T40 / 5-methyl-3-[4-(piperazin-1-ylmethyl)phenyl]isoquinolin-1(2H)-one


Mass: 333.427 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H23N3O
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 101 / 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: 2.34 Å3/Da / Density % sol: 47.42 % / Description: NONE
Crystal growpH: 6
Details: 0.1 M MES PH 6.0, 0.1 M AMMONIUM TARTARATE, 12-16% W/V PEG 3350

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 29, 2011
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.52→33.8 Å / Num. obs: 9367 / % possible obs: 98.4 % / Observed criterion σ(I): 0 / Redundancy: 2.9 % / Biso Wilson estimate: 57.38 Å2 / Rmerge(I) obs: 0.07 / Net I/σ(I): 11.6
Reflection shellResolution: 2.52→2.62 Å / Redundancy: 2.9 % / Rmerge(I) obs: 0.62 / Mean I/σ(I) obs: 2 / % possible all: 99.5

-
Processing

Software
NameVersionClassification
BUSTER2.10.1refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 2R5F

2r5f


Resolution: 2.52→33.8 Å / Cor.coef. Fo:Fc: 0.9444 / Cor.coef. Fo:Fc free: 0.9207 / SU R Cruickshank DPI: 0.389 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.45 / SU Rfree Blow DPI: 0.246 / SU Rfree Cruickshank DPI: 0.243
RfactorNum. reflection% reflectionSelection details
Rfree0.2176 478 5.1 %RANDOM
Rwork0.1662 ---
obs0.1688 9364 97.17 %-
Displacement parametersBiso mean: 41.19 Å2
Baniso -1Baniso -2Baniso -3
1--0.4897 Å20 Å20 Å2
2--8.5743 Å20 Å2
3----8.0846 Å2
Refine analyzeLuzzati coordinate error obs: 0.268 Å
Refinement stepCycle: LAST / Resolution: 2.52→33.8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1634 0 66 101 1801
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.011744HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.082333HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d798SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes40HARMONIC2
X-RAY DIFFRACTIONt_gen_planes279HARMONIC5
X-RAY DIFFRACTIONt_it1744HARMONIC20
X-RAY DIFFRACTIONt_nbd0SEMIHARMONIC5
X-RAY DIFFRACTIONt_omega_torsion3.54
X-RAY DIFFRACTIONt_other_torsion3.19
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion209SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies1HARMONIC1
X-RAY DIFFRACTIONt_utility_distance6HARMONIC1
X-RAY DIFFRACTIONt_utility_angle6HARMONIC1
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact1988SEMIHARMONIC4
LS refinement shellResolution: 2.52→2.82 Å / Total num. of bins used: 5
RfactorNum. reflection% reflection
Rfree0.2754 130 4.86 %
Rwork0.2154 2543 -
all0.2184 2673 -
obs--97.17 %

+
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