[English] 日本語
Yorodumi
- PDB-6vkq: Crystal Structure of human PARP-1 CAT domain bound to inhibitor EB-47 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6vkq
TitleCrystal Structure of human PARP-1 CAT domain bound to inhibitor EB-47
ComponentsPoly [ADP-ribose] polymerase 1
KeywordsTRANSFERASE/INHIBITOR / PARP-1 / poly(ADP-ribose) polymerase / PARP inhibitor / PARP1 / ARTD1 / TRANSFERASE / TRANSFERASE-INHIBITOR complex
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 / protein auto-ADP-ribosylation / negative regulation of telomere maintenance via telomere lengthening / 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 / NAD+-protein-glutamate ADP-ribosyltransferase activity / positive regulation of cardiac muscle hypertrophy / 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 / macrophage differentiation / site of DNA damage / Transferases; Glycosyltransferases; Pentosyltransferases / negative regulation of transcription elongation by RNA polymerase II / POLB-Dependent Long Patch Base Excision Repair / positive regulation of SMAD protein signal transduction / NAD+ poly-ADP-ribosyltransferase activity / 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 / Downregulation of SMAD2/3:SMAD4 transcriptional activity / enzyme activator 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 / histone deacetylase binding / Formation of Incision Complex in GG-NER / cellular response to insulin stimulus / cellular response to amyloid-beta / NAD binding / 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 / DNA damage response / ubiquitin protein ligase binding / 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 / 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 / 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 / Alpha Beta
Similarity search - Domain/homology
Chem-UHB / Poly [ADP-ribose] polymerase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.9 Å
AuthorsSteffen, J.D. / Pascal, J.M.
Funding support Canada, 1items
OrganizationGrant numberCountry
Canadian Institutes of Health Research (CIHR)BMA342854 Canada
CitationJournal: Science / Year: 2020
Title: Structural basis for allosteric PARP-1 retention on DNA breaks.
Authors: Zandarashvili, L. / Langelier, M.F. / Velagapudi, U.K. / Hancock, M.A. / Steffen, J.D. / Billur, R. / Hannan, Z.M. / Wicks, A.J. / Krastev, D.B. / Pettitt, S.J. / Lord, C.J. / Talele, T.T. / ...Authors: Zandarashvili, L. / Langelier, M.F. / Velagapudi, U.K. / Hancock, M.A. / Steffen, J.D. / Billur, R. / Hannan, Z.M. / Wicks, A.J. / Krastev, D.B. / Pettitt, S.J. / Lord, C.J. / Talele, T.T. / Pascal, J.M. / Black, B.E.
History
DepositionJan 21, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 17, 2020Provider: repository / Type: Initial release
Revision 1.1Oct 11, 2023Group: 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 / struct_ncs_dom_lim
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id
Revision 1.2Nov 20, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Poly [ADP-ribose] polymerase 1
B: Poly [ADP-ribose] polymerase 1
C: Poly [ADP-ribose] polymerase 1
D: Poly [ADP-ribose] polymerase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)169,59320
Polymers166,2904
Non-polymers3,30316
Water00
1
A: Poly [ADP-ribose] polymerase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,3985
Polymers41,5721
Non-polymers8264
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Poly [ADP-ribose] polymerase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,3985
Polymers41,5721
Non-polymers8264
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: Poly [ADP-ribose] polymerase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,3985
Polymers41,5721
Non-polymers8264
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: Poly [ADP-ribose] polymerase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,3985
Polymers41,5721
Non-polymers8264
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)140.219, 130.310, 101.870
Angle α, β, γ (deg.)90.000, 111.250, 90.000
Int Tables number5
Space group name H-MC121
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B
12A
22C
13A
23D
14B
24C
15B
25D
16C
26D

NCS domain segments:

Component-ID: _ / Beg auth comp-ID: LYS / Beg label comp-ID: LYS / End auth comp-ID: THR / End label comp-ID: THR / Refine code: _ / Auth seq-ID: 664 - 1011 / Label seq-ID: 25 - 372

Dom-IDEns-IDAuth asym-IDLabel asym-ID
11AA
21BB
12AA
22CC
13AA
23DD
14BB
24CC
15BB
25DD
16CC
26DD

NCS ensembles :
ID
1
2
3
4
5
6

-
Components

#1: Protein
Poly [ADP-ribose] polymerase 1 / PARP-1 / ADP-ribosyltransferase diphtheria toxin-like 1 / ARTD1 / DNA ADP-ribosyltransferase PARP1 ...PARP-1 / ADP-ribosyltransferase diphtheria toxin-like 1 / ARTD1 / DNA ADP-ribosyltransferase PARP1 / NAD(+) ADP-ribosyltransferase 1 / ADPRT 1 / Poly[ADP-ribose] synthase 1 / Protein poly-ADP-ribosyltransferase PARP1


Mass: 41572.461 Da / Num. of mol.: 4 / Fragment: catalytic domain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PARP1, ADPRT, PPOL / Production host: Escherichia coli (E. coli)
References: UniProt: P09874, NAD+ ADP-ribosyltransferase, Transferases; Glycosyltransferases; Pentosyltransferases
#2: Chemical
ChemComp-UHB / 2-[4-[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]carbonylpiperazin-1-yl]-N-(1-oxidanylidene-2,3-dihydroisoindol-4-yl)ethanamide


Mass: 537.528 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C24H27N9O6 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: SO4
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.61 Å3/Da / Density % sol: 52.84 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop / pH: 8 / Details: 2M Ammonium Sulfate, 5% PEG 400, 100 mM Tris pH 8

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 12.3.1 / Wavelength: 1.1158 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Aug 1, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.1158 Å / Relative weight: 1
ReflectionResolution: 2.9→94.943 Å / Num. all: 37721 / Num. obs: 37721 / % possible obs: 99.7 % / Redundancy: 5.6 % / Rpim(I) all: 0.057 / Rrim(I) all: 0.137 / Rsym value: 0.125 / Net I/av σ(I): 5.2 / Net I/σ(I): 8.3 / Num. measured all: 212738
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique obsRpim(I) allRrim(I) allRsym valueNet I/σ(I) obs% possible all
2.9-3.065.50.651.23031554720.30.7170.652.199.7
3.06-3.245.70.3542.12961852140.160.3890.3543.599.8
3.24-3.475.70.2363.12786748580.1060.2590.2365.399.9
3.47-3.745.70.1694.32618945890.0760.1850.1697.3100
3.74-4.15.70.13152392341780.0590.1440.1319.599.7
4.1-4.595.50.115.92062937850.0510.1210.111299.4
4.59-5.2950.0877.11654433290.0430.0970.08712.999.2
5.29-6.485.80.0847.61657528630.0380.0930.08411.599.9
6.48-9.176.20.05910.21370122140.0260.0650.05916.5100
9.17-47.4726.10.05112.4737712190.0220.0560.05121.198.8

-
Processing

Software
NameVersionClassification
MOSFLMdata reduction
SCALA3.3.22data scaling
REFMAC5.8.0257refinement
PDB_EXTRACT3.25data extraction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5ds3

5ds3


Resolution: 2.9→20 Å / Cor.coef. Fo:Fc: 0.855 / Cor.coef. Fo:Fc free: 0.826 / SU B: 51.483 / SU ML: 0.475 / SU R Cruickshank DPI: 0.545 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.579
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.3531 1903 5.1 %RANDOM
Rwork0.3233 ---
obs0.3248 35580 98.99 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 171.93 Å2 / Biso mean: 78.53 Å2 / Biso min: 25.22 Å2
Baniso -1Baniso -2Baniso -3
1-2.07 Å20 Å21.69 Å2
2--2.2 Å20 Å2
3----4.29 Å2
Refinement stepCycle: final / Resolution: 2.9→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10694 0 216 0 10910
Biso mean--70.41 --
Num. residues----1360
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0040.01311118
X-RAY DIFFRACTIONr_bond_other_d0.0010.01710490
X-RAY DIFFRACTIONr_angle_refined_deg1.3961.63415035
X-RAY DIFFRACTIONr_angle_other_deg1.0491.59424466
X-RAY DIFFRACTIONr_dihedral_angle_1_deg8.13851352
X-RAY DIFFRACTIONr_dihedral_angle_2_deg38.05423.913506
X-RAY DIFFRACTIONr_dihedral_angle_3_deg20.681152031
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.8771541
X-RAY DIFFRACTIONr_chiral_restr0.0510.21440
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0212538
X-RAY DIFFRACTIONr_gen_planes_other0.0010.022089
Refine LS restraints NCS

Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Weight position: 0.05

Ens-IDDom-IDAuth asym-IDNumberRms dev position (Å)
11A107320
12B107320
21A107230
22C107230
31A107240
32D107240
41B107200
42C107200
51B107190.01
52D107190.01
61C107250
62D107250
LS refinement shellResolution: 2.9→2.974 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.387 124 -
Rwork0.388 2573 -
all-2697 -
obs--99.3 %
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)
15.5403-0.4121-0.69033.40090.05993.94860.01780.2497-0.8005-0.5149-0.21060.39970.6829-0.69310.19280.2403-0.1096-0.00180.1544-0.09440.212828.1267-23.973375.7966
22.0442-1.3604-1.51151.02211.02531.1389-0.27690.1298-0.3873-0.16250.04110.45140.1610.03240.23581.5894-0.10570.09430.8648-0.02121.665643.5282-43.780665.3193
33.7991-0.03050.06894.9811.10025.1388-0.08410.59270.4317-0.2368-0.05440.7086-0.7858-0.56660.13850.20930.1358-0.060.24060.04430.15649.03319.882495.7814
40.2670.35740.40690.91370.80140.78660.0394-0.01170.3769-0.3257-0.36830.1328-0.0927-0.35270.32891.04370.2159-0.1662.0481-0.05691.3618-3.9108-0.740974.2849
54.6468-0.1840.76813.9899-0.37316.60680.0726-0.13670.7717-0.1073-0.0967-0.6511-0.86090.60270.02410.1794-0.13160.0380.1073-0.01160.231231.50220.4272131.7383
60.1126-0.32630.33061.3415-1.16171.1576-0.04250.1212-0.00120.1960.1685-0.3344-0.37350.0411-0.12611.8892-0.23170.0730.9661-0.07941.656827.309340.2401113.5208
74.23340.8072-0.73585.3119-0.774.9787-0.2232-0.0668-0.7130.30160.1271-0.70060.59481.01850.09610.13860.16940.02460.25190.0110.230531.9964-13.566159.1731
80.54120.5952-0.35760.8219-0.49710.31470.13540.0035-0.234-0.2352-0.181-0.1810.11580.22720.04550.99890.1099-0.1541.56750.04721.384256.1047-3.0343151.9365
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A664 - 689
2X-RAY DIFFRACTION1A790 - 1011
3X-RAY DIFFRACTION2A690 - 781
4X-RAY DIFFRACTION3B664 - 689
5X-RAY DIFFRACTION3B790 - 1011
6X-RAY DIFFRACTION4B690 - 781
7X-RAY DIFFRACTION5C664 - 689
8X-RAY DIFFRACTION5C790 - 1011
9X-RAY DIFFRACTION6C690 - 781
10X-RAY DIFFRACTION7D664 - 689
11X-RAY DIFFRACTION7D790 - 1011
12X-RAY DIFFRACTION8D690 - 781

+
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