[English] 日本語
Yorodumi- PDB-4hhy: Crystal structure of PARP catalytic domain in complex with novel ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4hhy | ||||||
---|---|---|---|---|---|---|---|
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 / 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: 2.3637 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 |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4hhy.cif.gz | 271.6 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4hhy.ent.gz | 219.6 KB | Display | PDB format |
PDBx/mmJSON format | 4hhy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4hhy_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 4hhy_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 4hhy_validation.xml.gz | 53.4 KB | Display | |
Data in CIF | 4hhy_validation.cif.gz | 70.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hh/4hhy ftp://data.pdbj.org/pub/pdb/validation_reports/hh/4hhy | HTTPS FTP |
-Related structure data
Related structure data | 4hhzC 3gjwS S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
2 |
| ||||||||
3 |
| ||||||||
4 |
| ||||||||
Unit cell |
|
-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-15R / ( #3: Chemical | #4: Chemical | ChemComp-PEG / | #5: Water | ChemComp-HOH / | |
---|
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.52 Å3/Da / Density % sol: 51.24 % |
---|---|
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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL17U / Wavelength: 0.979 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC Quantum Q315r / Detector: CCD / Date: Mar 22, 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: 2.28→43.61 Å / Num. obs: 137838 / % possible obs: 97.5 % / Observed criterion σ(I): -3 / Biso Wilson estimate: 52.413 Å2 / Rmerge(I) obs: 0.069 / Net I/σ(I): 12.92 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
|
-Phasing
Phasing | Method: molecular replacement | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Phasing MR | Model details: Phaser MODE: MR_AUTO
|
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 3GJW Resolution: 2.3637→43.606 Å / Occupancy max: 1 / Occupancy min: 1 / SU ML: 0.39 / σ(F): 1.34 / Phase error: 32.76 / Stereochemistry target values: ML
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 22.4082 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.3637→43.606 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
|