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Yorodumi- PDB-4hhz: Crystal structure of PARP catalytic domain in complex with novel ... -
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-Basic information
Entry | Database: PDB / ID: 4hhz | ||||||
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Title | Crystal structure of PARP catalytic domain in complex with novel inhibitors | ||||||
Components | Poly [ADP-ribose] polymerase 1 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / Polymerase / 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 / NAD DNA ADP-ribosyltransferase activity / NAD+-protein-aspartate ADP-ribosyltransferase activity / NAD+-protein-glutamate ADP-ribosyltransferase activity / mitochondrial DNA metabolic process / DNA ADP-ribosylation / regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / signal transduction involved in regulation of gene expression / positive regulation of necroptotic process / regulation of catalytic activity / ATP generation from poly-ADP-D-ribose / replication fork reversal / transcription regulator activator activity / HDR through MMEJ (alt-NHEJ) / 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 / positive regulation of mitochondrial depolarization / response to aldosterone / mitochondrial DNA repair / 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 / R-SMAD binding / positive regulation of SMAD protein signal transduction / macrophage differentiation / protein autoprocessing / decidualization / Transferases; Glycosyltransferases; Pentosyltransferases / positive regulation of double-strand break repair via homologous recombination / NAD+-protein poly-ADP-ribosyltransferase activity / POLB-Dependent Long Patch Base Excision Repair / SUMOylation of DNA damage response and repair proteins / nucleosome binding / protein localization to chromatin / negative regulation of innate immune response / telomere maintenance / nucleotidyltransferase activity / mitochondrion organization / transforming growth factor beta receptor signaling pathway / cellular response to nerve growth factor stimulus / nuclear estrogen receptor binding / response to gamma radiation / protein-DNA complex / Downregulation of SMAD2/3:SMAD4 transcriptional activity / DNA Damage Recognition in GG-NER / protein modification process / Dual Incision in GG-NER / Formation of Incision Complex in GG-NER / histone deacetylase binding / positive regulation of protein localization to nucleus / cellular response to amyloid-beta / cellular response to insulin stimulus / regulation of protein localization / cellular response to UV / NAD binding / double-strand break repair / nuclear envelope / 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 / chromosome, telomeric region / damaged DNA binding / nuclear body / DNA repair / innate immune response / negative regulation of DNA-templated transcription / apoptotic process / ubiquitin protein ligase binding / DNA damage response / chromatin binding / chromatin / nucleolus / protein kinase binding / enzyme binding / negative regulation of transcription by RNA polymerase II / protein homodimerization activity Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.7199 Å | ||||||
Authors | Liu, Q.F. / Chen, T.T. / Xu, Y.C. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2013 Title: Design, Synthesis, and Biological Evaluation of a Series of Benzo[de][1,7]naphthyridin-7(8H)-ones Bearing a Functionalized Longer Chain Appendage as Novel PARP1 Inhibitors. Authors: Ye, N. / Chen, C.H. / Chen, T. / Song, Z. / He, J.X. / Huan, X.J. / Song, S.S. / Liu, Q. / Chen, Y. / Ding, J. / Xu, Y. / Miao, Z.H. / Zhang, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4hhz.cif.gz | 271.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4hhz.ent.gz | 220.9 KB | Display | PDB format |
PDBx/mmJSON format | 4hhz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4hhz_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 4hhz_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 4hhz_validation.xml.gz | 51.3 KB | Display | |
Data in CIF | 4hhz_validation.cif.gz | 67.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hh/4hhz ftp://data.pdbj.org/pub/pdb/validation_reports/hh/4hhz | HTTPS FTP |
-Related structure data
Related structure data | 4hhyC 3gjwS 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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Unit cell |
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-Components
#1: Protein | Mass: 39580.262 Da / Num. of mol.: 4 / Fragment: UNP Residues 660-1101 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ADPRT, PARP1, PPOL / Plasmid: Pgex-6p-1 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P09874, NAD+ ADP-ribosyltransferase #2: Chemical | ChemComp-15S / #3: Chemical | #4: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.48 Å3/Da / Density % sol: 50.43 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8 Details: 0.1M TRIS pH 8.0, 1% PEG400, 1.9M (NH4)2SO4, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL17U / Wavelength: 0.979 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC Quantum Q315r / Detector: CCD / Date: Apr 17, 2012 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.979 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.22→48.431 Å / Num. obs: 77829 / % possible obs: 99.1 % / Observed criterion σ(I): -3 / Biso Wilson estimate: 50.167 Å2 / Rmerge(I) obs: 0.18 / Net I/σ(I): 7.2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR | Model details: Phaser MODE: MR_AUTO
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 3GJW Resolution: 2.7199→48.431 Å / Occupancy max: 1 / Occupancy min: 1 / SU ML: 0.4 / σ(F): 2.01 / Phase error: 28.27 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 24.843 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.7199→48.431 Å
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Refine LS restraints |
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LS refinement shell |
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