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Yorodumi- PDB-6nrg: Crystal Structure of human PARP-1 ART domain bound to inhibitor UTT57 -
+Open data
-Basic information
Entry | Database: PDB / ID: 6nrg | ||||||
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Title | Crystal Structure of human PARP-1 ART domain bound to inhibitor UTT57 | ||||||
Components | Poly [ADP-ribose] polymerase 1 | ||||||
Keywords | transferase/transferase inhibitor / PARP-1 / poly(ADP-ribose) polymerase / PARP inhibitor / PARP1 / ARTD1 / TRANSFERASE / 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 / regulation of base-excision repair / positive regulation of myofibroblast differentiation / negative regulation of ATP biosynthetic process / NAD+-protein-tyrosine ADP-ribosyltransferase activity / NAD+-protein-histidine ADP-ribosyltransferase activity / carbohydrate biosynthetic process / positive regulation of single strand break repair ...NAD+-histone H2BS6 serine ADP-ribosyltransferase activity / NAD+-histone H3S10 serine ADP-ribosyltransferase activity / NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity / regulation of base-excision repair / positive regulation of myofibroblast differentiation / negative regulation of ATP biosynthetic process / NAD+-protein-tyrosine ADP-ribosyltransferase activity / NAD+-protein-histidine ADP-ribosyltransferase activity / carbohydrate biosynthetic process / positive regulation of single strand break repair / regulation of circadian sleep/wake cycle, non-REM sleep / vRNA Synthesis / negative regulation of adipose tissue development / NAD+-protein-serine ADP-ribosyltransferase activity / regulation of catalytic activity / NAD DNA ADP-ribosyltransferase activity / NAD+-protein-aspartate ADP-ribosyltransferase activity / NAD+-protein-glutamate ADP-ribosyltransferase activity / DNA ADP-ribosylation / mitochondrial DNA metabolic process / regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / signal transduction involved in regulation of gene expression / positive regulation of necroptotic process / ATP generation from poly-ADP-D-ribose / replication fork reversal / transcription regulator activator activity / HDR through MMEJ (alt-NHEJ) / R-SMAD binding / positive regulation of DNA-templated transcription, elongation / positive regulation of intracellular estrogen receptor signaling pathway / NAD+ ADP-ribosyltransferase / cellular response to zinc ion / negative regulation of telomere maintenance via telomere lengthening / protein auto-ADP-ribosylation / response to aldosterone / mitochondrial DNA repair / positive regulation of mitochondrial depolarization / negative regulation of cGAS/STING signaling pathway / protein poly-ADP-ribosylation / positive regulation of cardiac muscle hypertrophy / negative regulation of transcription elongation by RNA polymerase II / nuclear replication fork / NAD+-protein ADP-ribosyltransferase activity / site of DNA damage / positive regulation of SMAD protein signal transduction / macrophage differentiation / protein autoprocessing / decidualization / NAD+-protein poly-ADP-ribosyltransferase activity / Transferases; Glycosyltransferases; Pentosyltransferases / positive regulation of double-strand break repair via homologous recombination / POLB-Dependent Long Patch Base Excision Repair / nucleosome binding / SUMOylation of DNA damage response and repair proteins / protein localization to chromatin / negative regulation of innate immune response / telomere maintenance / nucleotidyltransferase activity / transforming growth factor beta receptor signaling pathway / cellular response to nerve growth factor stimulus / mitochondrion organization / nuclear estrogen receptor binding / protein-DNA complex / response to gamma radiation / Downregulation of SMAD2/3:SMAD4 transcriptional activity / DNA Damage Recognition in GG-NER / protein modification process / cellular response to insulin stimulus / Dual Incision in GG-NER / histone deacetylase binding / Formation of Incision Complex in GG-NER / positive regulation of protein localization to nucleus / cellular response to amyloid-beta / nuclear envelope / NAD binding / regulation of protein localization / cellular response to UV / double-strand break repair / site of double-strand break / positive regulation of canonical NF-kappaB signal transduction / cellular response to oxidative stress / chromosome, telomeric region / transcription regulator complex / RNA polymerase II-specific DNA-binding transcription factor binding / transcription by RNA polymerase II / damaged DNA binding / nuclear body / DNA repair / innate immune response / negative regulation of DNA-templated transcription / chromatin binding / DNA damage response / ubiquitin protein ligase binding / chromatin / nucleolus / protein kinase binding / apoptotic process / enzyme binding / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.7 Å | ||||||
Authors | Langelier, M.F. / Pascal, J.M. | ||||||
Funding support | Canada, 1items
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Citation | Journal: J.Med.Chem. / Year: 2019 Title: Design and Synthesis of Poly(ADP-ribose) Polymerase Inhibitors: Impact of Adenosine Pocket-Binding Motif Appendage to the 3-Oxo-2,3-dihydrobenzofuran-7-carboxamide on Potency and Selectivity. Authors: Velagapudi, U.K. / Langelier, M.F. / Delgado-Martin, C. / Diolaiti, M.E. / Bakker, S. / Ashworth, A. / Patel, B.A. / Shao, X. / Pascal, J.M. / Talele, T.T. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6nrg.cif.gz | 120 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6nrg.ent.gz | 90 KB | Display | PDB format |
PDBx/mmJSON format | 6nrg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6nrg_validation.pdf.gz | 721.6 KB | Display | wwPDB validaton report |
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Full document | 6nrg_full_validation.pdf.gz | 722.4 KB | Display | |
Data in XML | 6nrg_validation.xml.gz | 13.3 KB | Display | |
Data in CIF | 6nrg_validation.cif.gz | 18.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nr/6nrg ftp://data.pdbj.org/pub/pdb/validation_reports/nr/6nrg | HTTPS FTP |
-Related structure data
Related structure data | 6nrfC 6nrhC 6nriC 6nrjC 6bhvS C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 30003.275 Da / Num. of mol.: 1 / Fragment: ADP-ribosyltransferase (ART) domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PARP1, ADPRT, PPOL / Plasmid: pET28 / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta2(DE3) References: UniProt: P09874, NAD+ ADP-ribosyltransferase, Transferases; Glycosyltransferases; Pentosyltransferases | ||||
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#2: Chemical | ChemComp-KYY / | ||||
#3: Chemical | ChemComp-SO4 / #4: Chemical | #5: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.5 Å3/Da / Density % sol: 50.73 % |
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Crystal grow | Temperature: 298 K / Method: evaporation / pH: 7.5 Details: ~20% PEG 3350, 0.2 M ammonium sulfate or sodium citrate, 100 mM Hepes pH 7.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.979 Å | ||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Feb 8, 2018 | ||||||||||||||||||||||||
Radiation | Monochromator: ACCEL/BRUKER double crystal monochromator (DCM), Si(111) Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.979 Å / Relative weight: 1 | ||||||||||||||||||||||||
Reflection | Resolution: 1.7→47.72 Å / Num. obs: 33747 / % possible obs: 100 % / Redundancy: 27.9 % / CC1/2: 1 / Rmerge(I) obs: 0.069 / Rpim(I) all: 0.013 / Rrim(I) all: 0.071 / Net I/σ(I): 24.7 / Num. measured all: 940705 / Scaling rejects: 40 | ||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDBID 6BHV Resolution: 1.7→47.72 Å / Cor.coef. Fo:Fc: 0.976 / Cor.coef. Fo:Fc free: 0.969 / SU B: 3.335 / SU ML: 0.056 / SU R Cruickshank DPI: 0.0832 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.083 / ESU R Free: 0.082 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1.3 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 117.79 Å2 / Biso mean: 38.602 Å2 / Biso min: 22.37 Å2
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Refinement step | Cycle: final / Resolution: 1.7→47.72 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.7→1.744 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Origin x: 25.0317 Å / Origin y: -4.0606 Å / Origin z: 18.7876 Å
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