[English] 日本語
Yorodumi
- PDB-4w6e: Human Tankyrase 1 with small molecule inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4w6e
TitleHuman Tankyrase 1 with small molecule inhibitor
ComponentsTankyrase-1
KeywordsTRANSFERASE/INHIBITOR / Tankyrase Inhibitor Small Molecule / TRANSFERASE-INHIBITOR complex
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 / positive regulation of telomere capping / NAD+-protein ADP-ribosyltransferase activity / NAD+ ADP-ribosyltransferase activity / Transferases; Glycosyltransferases; Pentosyltransferases / 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-3J5 / Poly [ADP-ribose] polymerase tankyrase-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.95 Å
AuthorsKazmirski, S.L. / Johannes, J. / Boriack-Sjodin, P.A. / Howard, T.
CitationJournal: Acs Med.Chem.Lett. / Year: 2015
Title: Pyrimidinone nicotinamide mimetics as selective tankyrase and wnt pathway inhibitors suitable for in vivo pharmacology.
Authors: Johannes, J.W. / Almeida, L. / Barlaam, B. / Boriack-Sjodin, P.A. / Casella, R. / Croft, R.A. / Dishington, A.P. / Gingipalli, L. / Gu, C. / Hawkins, J.L. / Holmes, J.L. / Howard, T. / ...Authors: Johannes, J.W. / Almeida, L. / Barlaam, B. / Boriack-Sjodin, P.A. / Casella, R. / Croft, R.A. / Dishington, A.P. / Gingipalli, L. / Gu, C. / Hawkins, J.L. / Holmes, J.L. / Howard, T. / Huang, J. / Ioannidis, S. / Kazmirski, S. / Lamb, M.L. / McGuire, T.M. / Moore, J.E. / Ogg, D. / Patel, A. / Pike, K.G. / Pontz, T. / Robb, G.R. / Su, N. / Wang, H. / Wu, X. / Zhang, H.J. / Zhang, Y. / Zheng, X. / Wang, T.
History
DepositionAug 20, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 13, 2015Provider: repository / Type: Initial release
Revision 1.1Dec 27, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description / Source and taxonomy / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / entity_src_gen / pdbx_database_status / pdbx_struct_assembly / pdbx_struct_oper_list / refine_hist / struct_keywords
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity_src_gen.pdbx_alt_source_flag / _pdbx_database_status.pdb_format_compatible / _pdbx_struct_assembly.oligomeric_details / _pdbx_struct_oper_list.symmetry_operation / _refine_hist.number_atoms_solvent / _refine_hist.number_atoms_total / _refine_hist.pdbx_number_atoms_ligand / _refine_hist.pdbx_number_atoms_nucleic_acid / _struct_keywords.text

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Tankyrase-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)24,7483
Polymers24,2281
Non-polymers5212
Water4,071226
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)80.774, 81.847, 83.309
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number24
Space group name H-MI212121

-
Components

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


Mass: 24227.508 Da / Num. of mol.: 1 / Fragment: PARP DOMAIN
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
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-3J5 / 2-(4-{6-[(3S)-3,4-dimethylpiperazin-1-yl]-4-methylpyridin-3-yl}phenyl)-8-(hydroxymethyl)quinazolin-4(3H)-one


Mass: 455.551 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C27H29N5O2
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 226 / 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: 2.86 Å3/Da / Density % sol: 56.92 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 5 / Details: 1.4 Sodium Formate, 0.1 Sodium Acetate pH 5

-
Data collection

DiffractionMean temperature: 93 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E+ SUPERBRIGHT / Wavelength: 1.54 Å
DetectorType: RIGAKU SATURN 944+ / Detector: CCD / Date: Apr 20, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 1.95→58.38 Å / Num. obs: 20488 / % possible obs: 100 % / Redundancy: 6.82 % / Biso Wilson estimate: 36.93 Å2 / Rsym value: 0.068 / Net I/σ(I): 11.2
Reflection shellResolution: 1.95→2.02 Å / Redundancy: 5.31 % / Rmerge(I) obs: 0.467 / Mean I/σ(I) obs: 2.4 / % possible all: 100

-
Processing

SoftwareName: BUSTER / Version: 2.11.5 / Classification: refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.95→40.39 Å / Cor.coef. Fo:Fc: 0.9482 / Cor.coef. Fo:Fc free: 0.9128 / SU R Cruickshank DPI: 0.156 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.17 / SU Rfree Blow DPI: 0.159 / SU Rfree Cruickshank DPI: 0.153
RfactorNum. reflection% reflectionSelection details
Rfree0.2541 1044 5.11 %RANDOM
Rwork0.2047 ---
obs0.2071 20430 99.71 %-
Displacement parametersBiso mean: 40.85 Å2
Baniso -1Baniso -2Baniso -3
1-6.0787 Å20 Å20 Å2
2---0.0817 Å20 Å2
3----5.997 Å2
Refine analyzeLuzzati coordinate error obs: 0.262 Å
Refinement stepCycle: 1 / Resolution: 1.95→40.39 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1689 0 35 226 1950
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0091769HARMONIC2
X-RAY DIFFRACTIONt_angle_deg12381HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d619SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes40HARMONIC2
X-RAY DIFFRACTIONt_gen_planes261HARMONIC5
X-RAY DIFFRACTIONt_it1769HARMONIC20
X-RAY DIFFRACTIONt_nbd1SEMIHARMONIC5
X-RAY DIFFRACTIONt_omega_torsion3.79
X-RAY DIFFRACTIONt_other_torsion16.71
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion215SEMIHARMONIC5
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_contact2132SEMIHARMONIC4
LS refinement shellResolution: 1.95→2.06 Å / Total num. of bins used: 10
RfactorNum. reflection% reflection
Rfree0.2185 149 5.09 %
Rwork0.2058 2777 -
all0.2065 2926 -
obs--99.71 %
Refinement TLS params.Method: refined / Origin x: 17.4764 Å / Origin y: 14.0783 Å / Origin z: -19.37 Å
111213212223313233
T-0.0867 Å2-0.0107 Å20.0059 Å2--0.0701 Å2-0.0024 Å2---0.0427 Å2
L2.1592 °20.1495 °20.6585 °2-0.9717 °2-0.0594 °2--1.1953 °2
S-0.0964 Å °0.1835 Å °0.046 Å °0.0527 Å °0.0358 Å °0.0579 Å °-0.0263 Å °0.1824 Å °0.0606 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