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Yorodumi- PDB-6nrf: Crystal Structure of human PARP-1 ART domain bound to inhibitor UTT103 -
+Open data
-Basic information
Entry | Database: PDB / ID: 6nrf | ||||||
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Title | Crystal Structure of human PARP-1 ART domain bound to inhibitor UTT103 | ||||||
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 / positive regulation of myofibroblast differentiation / regulation of base-excision repair / negative regulation of ATP biosynthetic process / NAD+-protein-tyrosine ADP-ribosyltransferase activity / NAD+-protein-histidine ADP-ribosyltransferase activity / positive regulation of single strand break repair / carbohydrate biosynthetic process ...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 / regulation of base-excision repair / negative regulation of ATP biosynthetic process / NAD+-protein-tyrosine ADP-ribosyltransferase activity / NAD+-protein-histidine ADP-ribosyltransferase activity / positive regulation of single strand break repair / carbohydrate biosynthetic process / regulation of circadian sleep/wake cycle, non-REM sleep / vRNA Synthesis / regulation of catalytic activity / NAD+-protein-serine ADP-ribosyltransferase activity / negative regulation of adipose tissue development / 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 / replication fork reversal / signal transduction involved in regulation of gene expression / positive regulation of necroptotic process / ATP generation from poly-ADP-D-ribose / transcription regulator activator activity / HDR through MMEJ (alt-NHEJ) / negative regulation of cGAS/STING signaling pathway / positive regulation of DNA-templated transcription, elongation / cellular response to zinc ion / positive regulation of intracellular estrogen receptor signaling pathway / NAD+ ADP-ribosyltransferase / negative regulation of telomere maintenance via telomere lengthening / protein auto-ADP-ribosylation / mitochondrial DNA repair / response to aldosterone / protein poly-ADP-ribosylation / positive regulation of mitochondrial depolarization / positive regulation of cardiac muscle hypertrophy / nuclear replication fork / negative regulation of transcription elongation by RNA polymerase II / NAD+-protein ADP-ribosyltransferase activity / site of DNA damage / R-SMAD binding / positive regulation of SMAD protein signal transduction / protein autoprocessing / macrophage differentiation / decidualization / NAD+-protein poly-ADP-ribosyltransferase activity / Transferases; Glycosyltransferases; Pentosyltransferases / nucleosome binding / positive regulation of double-strand break repair via homologous recombination / POLB-Dependent Long Patch Base Excision Repair / SUMOylation of DNA damage response and repair proteins / negative regulation of innate immune response / protein localization to chromatin / telomere maintenance / nucleotidyltransferase activity / transforming growth factor beta receptor signaling pathway / cellular response to nerve growth factor stimulus / protein-DNA complex / response to gamma radiation / mitochondrion organization / nuclear estrogen receptor binding / Downregulation of SMAD2/3:SMAD4 transcriptional activity / protein modification process / DNA Damage Recognition in GG-NER / Dual Incision in GG-NER / histone deacetylase binding / cellular response to insulin stimulus / Formation of Incision Complex in GG-NER / positive regulation of protein localization to nucleus / cellular response to amyloid-beta / cellular response to UV / NAD binding / double-strand break repair / nuclear envelope / regulation of protein localization / site of double-strand break / cellular response to oxidative stress / positive regulation of canonical NF-kappaB signal transduction / RNA polymerase II-specific DNA-binding transcription factor binding / transcription regulator complex / transcription by RNA polymerase II / damaged DNA binding / chromosome, telomeric region / nuclear body / innate immune response / DNA repair / negative regulation of DNA-templated transcription / DNA damage response / ubiquitin protein ligase binding / chromatin binding / chromatin / nucleolus / apoptotic process / protein kinase binding / negative regulation of transcription by RNA polymerase II / enzyme binding / protein homodimerization activity Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2 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 | 6nrf.cif.gz | 118.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6nrf.ent.gz | 87.9 KB | Display | PDB format |
PDBx/mmJSON format | 6nrf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6nrf_validation.pdf.gz | 719 KB | Display | wwPDB validaton report |
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Full document | 6nrf_full_validation.pdf.gz | 720.4 KB | Display | |
Data in XML | 6nrf_validation.xml.gz | 12.5 KB | Display | |
Data in CIF | 6nrf_validation.cif.gz | 17.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nr/6nrf ftp://data.pdbj.org/pub/pdb/validation_reports/nr/6nrf | HTTPS FTP |
-Related structure data
Related structure data | 6nrgC 6nrhC 6nriC 6nrjC 6bhvS S: Starting model for refinement C: citing same article (ref.) |
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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
-Protein , 1 types, 1 molecules A
#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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-Non-polymers , 5 types, 111 molecules
#2: Chemical | ChemComp-CIT / | ||
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#3: Chemical | ChemComp-DMS / | ||
#4: Chemical | ChemComp-KYV / | ||
#5: Chemical | #6: 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: 2.51 Å3/Da / Density % sol: 51.02 % |
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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: 2→47.79 Å / Num. obs: 21034 / % possible obs: 100 % / Redundancy: 24.5 % / Net I/σ(I): 16.4 |
Reflection shell | Resolution: 2→2.05 Å |
-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: 2→47.79 Å / Cor.coef. Fo:Fc: 0.965 / Cor.coef. Fo:Fc free: 0.95 / SU B: 10.557 / SU ML: 0.138 / SU R Cruickshank DPI: 0.166 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.166 / ESU R Free: 0.154 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.9 Å / Shrinkage radii: 0.9 Å / VDW probe radii: 1.3 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 89.61 Å2 / Biso mean: 41.997 Å2 / Biso min: 25.69 Å2
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Refinement step | Cycle: final / Resolution: 2→47.79 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2→2.052 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Origin x: 25.2114 Å / Origin y: -4.3762 Å / Origin z: 18.8033 Å
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