[English] 日本語
Yorodumi
- PDB-4und: HUMAN ARTD1 (PARP1) - CATALYTIC DOMAIN IN COMPLEX WITH INHIBITOR ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4und
TitleHUMAN ARTD1 (PARP1) - CATALYTIC DOMAIN IN COMPLEX WITH INHIBITOR TALAZOPARIB
ComponentsPOLY [ADP-RIBOSE] POLYMERASE 1
KeywordsTRANSFERASE / PROTEIN-INHIBITOR COMPLEX / ADP-RIBOSYLATION / DNA REPAIR
Function / homology
Function and homology information


NAD+-histone H2BS6 serine ADP-ribosyltransferase activity / NAD+-histone H3S10 serine ADP-ribosyltransferase activity / NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity / positive regulation of myofibroblast differentiation / negative regulation of ATP biosynthetic process / NAD+-protein-tyrosine ADP-ribosyltransferase activity / NAD+-protein-histidine ADP-ribosyltransferase activity / regulation of base-excision repair / positive regulation of single strand break repair / regulation of circadian sleep/wake cycle, non-REM sleep ...NAD+-histone H2BS6 serine ADP-ribosyltransferase activity / NAD+-histone H3S10 serine ADP-ribosyltransferase activity / NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity / positive regulation of myofibroblast differentiation / negative regulation of ATP biosynthetic process / NAD+-protein-tyrosine ADP-ribosyltransferase activity / NAD+-protein-histidine ADP-ribosyltransferase activity / regulation of base-excision repair / positive regulation of single strand break repair / regulation of circadian sleep/wake cycle, non-REM sleep / vRNA Synthesis / carbohydrate biosynthetic process / NAD+-protein-serine ADP-ribosyltransferase activity / negative regulation of adipose tissue development / NAD DNA ADP-ribosyltransferase activity / DNA ADP-ribosylation / mitochondrial DNA metabolic process / regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / replication fork reversal / ATP generation from poly-ADP-D-ribose / positive regulation of necroptotic process / transcription regulator activator activity / response to aldosterone / HDR through MMEJ (alt-NHEJ) / positive regulation of DNA-templated transcription, elongation / NAD+ ADP-ribosyltransferase / signal transduction involved in regulation of gene expression / negative regulation of telomere maintenance via telomere lengthening / protein auto-ADP-ribosylation / mitochondrial DNA repair / NAD+-protein-aspartate ADP-ribosyltransferase activity / protein poly-ADP-ribosylation / positive regulation of intracellular estrogen receptor signaling pathway / negative regulation of cGAS/STING signaling pathway / positive regulation of cardiac muscle hypertrophy / NAD+-protein-glutamate ADP-ribosyltransferase activity / positive regulation of mitochondrial depolarization / cellular response to zinc ion / NAD+-protein mono-ADP-ribosyltransferase activity / nuclear replication fork / decidualization / protein autoprocessing / R-SMAD binding / site of DNA damage / negative regulation of transcription elongation by RNA polymerase II / macrophage differentiation / Transferases; Glycosyltransferases; Pentosyltransferases / NAD+ poly-ADP-ribosyltransferase activity / positive regulation of SMAD protein signal transduction / POLB-Dependent Long Patch Base Excision Repair / SUMOylation of DNA damage response and repair proteins / positive regulation of double-strand break repair via homologous recombination / nucleosome binding / protein localization to chromatin / nucleotidyltransferase activity / telomere maintenance / transforming growth factor beta receptor signaling pathway / negative regulation of innate immune response / nuclear estrogen receptor binding / response to gamma radiation / mitochondrion organization / enzyme activator activity / Downregulation of SMAD2/3:SMAD4 transcriptional activity / protein-DNA complex / cellular response to nerve growth factor stimulus / DNA Damage Recognition in GG-NER / protein modification process / Dual Incision in GG-NER / positive regulation of protein localization to nucleus / Formation of Incision Complex in GG-NER / histone deacetylase binding / cellular response to insulin stimulus / NAD binding / cellular response to amyloid-beta / cellular response to UV / nuclear envelope / double-strand break repair / regulation of protein localization / site of double-strand break / cellular response to oxidative stress / transcription regulator complex / damaged DNA binding / RNA polymerase II-specific DNA-binding transcription factor binding / transcription by RNA polymerase II / chromosome, telomeric region / positive regulation of canonical NF-kappaB signal transduction / nuclear body / innate immune response / DNA repair / negative regulation of DNA-templated transcription / apoptotic process / ubiquitin protein ligase binding / DNA damage response / chromatin binding / protein kinase binding / chromatin / nucleolus / enzyme binding / negative regulation of transcription by RNA polymerase II / protein homodimerization activity
Similarity search - Function
Poly(ADP-ribose) polymerase, regulatory domain / Poly(ADP-ribose) Polymerase; domain 1 / Poly [ADP-ribose] polymerase / PADR1 domain / PADR1 domain superfamily / : / PADR1 domain, zinc ribbon fold / PADR1, N-terminal helical domain / PADR1 domain profile. / PADR1 ...Poly(ADP-ribose) polymerase, regulatory domain / Poly(ADP-ribose) Polymerase; domain 1 / Poly [ADP-ribose] polymerase / PADR1 domain / PADR1 domain superfamily / : / PADR1 domain, zinc ribbon fold / PADR1, N-terminal helical domain / PADR1 domain profile. / PADR1 / Zinc finger poly(ADP-ribose) polymerase (PARP)-type signature. / Zinc finger, PARP-type superfamily / Poly(ADP-ribose) polymerase and DNA-Ligase Zn-finger region / Zinc finger poly(ADP-ribose) polymerase (PARP)-type profile. / Poly(ADP-ribose) polymerase and DNA-Ligase Zn-finger region / Zinc finger, PARP-type / : / Poly(ADP-ribose) polymerase, regulatory domain / WGR domain / WGR domain superfamily / WGR domain / WGR domain profile. / Proposed nucleic acid binding domain / Poly(ADP-ribose) polymerase, regulatory domain superfamily / Poly(ADP-ribose) polymerase, regulatory domain / PARP alpha-helical domain profile. / Phosphoenolpyruvate Carboxykinase; domain 3 - #10 / Phosphoenolpyruvate Carboxykinase; domain 3 / BRCA1 C Terminus (BRCT) domain / Poly(ADP-ribose) polymerase catalytic domain / Poly(ADP-ribose) polymerase, catalytic domain / PARP catalytic domain profile. / breast cancer carboxy-terminal domain / BRCT domain profile. / BRCT domain / BRCT domain superfamily / Alpha-Beta Complex / Up-down Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-2YQ / Poly [ADP-ribose] polymerase 1
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsKarlberg, T. / Thorsell, A.G. / Ekblad, T. / Klepsch, M. / Pinto, A.F. / Tresaugues, L. / Moche, M. / Schuler, H.
CitationJournal: J. Med. Chem. / Year: 2017
Title: Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
Authors: Thorsell, A.G. / Ekblad, T. / Karlberg, T. / Low, M. / Pinto, A.F. / Tresaugues, L. / Moche, M. / Cohen, M.S. / Schuler, H.
History
DepositionMay 27, 2014Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 17, 2015Provider: repository / Type: Initial release
Revision 1.1Jan 18, 2017Group: Database references
Revision 1.2Mar 22, 2017Group: Database references
Revision 1.3Jan 10, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_site
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI ..._chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _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: POLY [ADP-RIBOSE] POLYMERASE 1
B: POLY [ADP-RIBOSE] POLYMERASE 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)84,5015
Polymers83,7172
Non-polymers7843
Water1,26170
1
A: POLY [ADP-RIBOSE] POLYMERASE 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,2392
Polymers41,8591
Non-polymers3801
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: POLY [ADP-RIBOSE] POLYMERASE 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,2623
Polymers41,8591
Non-polymers4032
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)103.455, 103.455, 168.539
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number92
Space group name H-MP41212

-
Components

#1: Protein POLY [ADP-RIBOSE] POLYMERASE 1 / PARP-1 / ADP-RIBOSYLTRANSFERASE DIPHTHERIA TOXIN-LIKE 1 / ARTD1 / NAD(+) ADP-RIBOSYLTRANSFERASE 1 / ...PARP-1 / ADP-RIBOSYLTRANSFERASE DIPHTHERIA TOXIN-LIKE 1 / ARTD1 / NAD(+) ADP-RIBOSYLTRANSFERASE 1 / ADPRT 1 / POLYADP-RIBOSE SYNTHASE 1 / POLY ADP-RIBOSE POLYMERASE 1


Mass: 41858.738 Da / Num. of mol.: 2 / Fragment: CATALYTIC DOMAIN, RESIDUES 662-1011
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PNIC-BSA4 / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / Variant (production host): ROSETTA / References: UniProt: P09874, NAD+ ADP-ribosyltransferase
#2: Chemical ChemComp-2YQ / (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one / Talazoparib


Mass: 380.351 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C19H14F2N6O
#3: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 70 / 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: 2.69 Å3/Da / Density % sol: 54 % / Description: NONE
Crystal growpH: 6.6 / Details: 39% PEGMME2000, 0.2M KSCN, 0.1M HEPES, pH 6.6

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.1 / Wavelength: 0.91841
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 20, 2014 / Details: MIRRORS
RadiationMonochromator: SI-111 DOUBLE CRYSTAL MONOCHROMATOR / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.91841 Å / Relative weight: 1
ReflectionResolution: 2.2→50 Å / Num. obs: 47155 / % possible obs: 99.9 % / Observed criterion σ(I): 0 / Redundancy: 14.8 % / Rmerge(I) obs: 0.09 / Net I/σ(I): 23.9
Reflection shellResolution: 2.2→2.28 Å / Redundancy: 15.4 % / Rmerge(I) obs: 0.93 / Mean I/σ(I) obs: 3.1 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
REFMAC5.7.0032refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 4GV7

4gv7


Resolution: 2.2→46.27 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.939 / SU B: 12.474 / SU ML: 0.153 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.257 / ESU R Free: 0.196 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
RfactorNum. reflection% reflectionSelection details
Rfree0.2464 2358 5 %RANDOM
Rwork0.22644 ---
obs0.22746 44803 99.98 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 60.941 Å2
Baniso -1Baniso -2Baniso -3
1-0.81 Å20 Å20 Å2
2--0.81 Å20 Å2
3----1.62 Å2
Refinement stepCycle: LAST / Resolution: 2.2→46.27 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms5550 0 57 70 5677
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0170.0195720
X-RAY DIFFRACTIONr_bond_other_d0.0040.025555
X-RAY DIFFRACTIONr_angle_refined_deg1.5481.9967728
X-RAY DIFFRACTIONr_angle_other_deg1.0043.00112849
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.1095703
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.67725.164244
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.942151059
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.1551522
X-RAY DIFFRACTIONr_chiral_restr0.0910.2858
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0216382
X-RAY DIFFRACTIONr_gen_planes_other0.0040.021222
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.8132.442818
X-RAY DIFFRACTIONr_mcbond_other1.8132.4392817
X-RAY DIFFRACTIONr_mcangle_it3.0533.653519
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it2.1892.72902
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.2→2.257 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.337 171 -
Rwork0.276 3254 -
obs--99.94 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.68250.3112-1.41440.4921-0.34522.37050.0429-0.13350.05260.0192-0.00440.0385-0.06490.0293-0.03860.2478-0.01230.0070.213-0.01220.271113.30372.33197.652
25.66451.99840.0946.44712.25886.45240.0574-0.0756-0.25450.4132-0.0506-0.0630.3489-0.4353-0.00690.39640.00810.10850.56520.05160.484-8.23966.159205.709
31.9590.2129-0.95741.68360.20183.2041-0.1250.4518-0.1736-0.16220.02190.13540.2326-0.67690.1030.1885-0.06240.01810.3922-0.06810.2607-6.47663.361189.009
40.7057-0.6083-0.35066.47021.87431.04740.02810.04030.06330.7766-0.0586-0.15670.158-0.01350.03040.3836-0.0141-0.04950.2128-0.01430.213225.80556.996216.067
51.8926-0.18630.10715.86870.60021.9916-0.1356-0.1186-0.13051.5480.125-0.36910.1320.12120.01070.67170.0788-0.09910.066-0.02220.169228.83242.972221.767
63.0688-0.91710.00484.26390.55211.5949-0.356-0.3805-0.3031.88110.24420.05610.2673-0.00330.11180.93160.11630.02240.05380.03750.195425.52135.962226.316
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A655 - 777
2X-RAY DIFFRACTION2A778 - 827
3X-RAY DIFFRACTION3A828 - 1010
4X-RAY DIFFRACTION4B662 - 827
5X-RAY DIFFRACTION5B828 - 936
6X-RAY DIFFRACTION6B937 - 1010

+
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