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Yorodumi- PDB-8pfp: Crystal structure of WRN helicase domain in complex with ATPgammaS -
+Open data
-Basic information
Entry | Database: PDB / ID: 8pfp | ||||||
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Title | Crystal structure of WRN helicase domain in complex with ATPgammaS | ||||||
Components | Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN | ||||||
Keywords | HYDROLASE / Inhibitor / Complex | ||||||
Function / homology | Function and homology information 3'-flap-structured DNA binding / positive regulation of strand invasion / telomeric G-quadruplex DNA binding / forked DNA-dependent helicase activity / positive regulation of hydrolase activity / 8-hydroxy-2'-deoxyguanosine DNA binding / telomeric D-loop binding / regulation of growth rate / telomere maintenance via semi-conservative replication / G-quadruplex DNA unwinding ...3'-flap-structured DNA binding / positive regulation of strand invasion / telomeric G-quadruplex DNA binding / forked DNA-dependent helicase activity / positive regulation of hydrolase activity / 8-hydroxy-2'-deoxyguanosine DNA binding / telomeric D-loop binding / regulation of growth rate / telomere maintenance via semi-conservative replication / G-quadruplex DNA unwinding / t-circle formation / telomeric D-loop disassembly / Y-form DNA binding / DNA 3'-5' helicase / four-way junction helicase activity / G-quadruplex DNA binding / MutLalpha complex binding / bubble DNA binding / Processive synthesis on the C-strand of the telomere / Impaired BRCA2 binding to PALB2 / Removal of the Flap Intermediate from the C-strand / protein localization to nucleolus / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Homologous DNA Pairing and Strand Exchange / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / response to UV-C / Resolution of D-loop Structures through Holliday Junction Intermediates / exonuclease activity / DNA duplex unwinding / HDR through Single Strand Annealing (SSA) / Impaired BRCA2 binding to RAD51 / DNA metabolic process / 3'-5' DNA helicase activity / DNA synthesis involved in DNA repair / replication fork processing / DNA unwinding involved in DNA replication / Presynaptic phase of homologous DNA pairing and strand exchange / replicative senescence / SUMOylation of DNA damage response and repair proteins / four-way junction DNA binding / isomerase activity / cellular response to starvation / 3'-5' exonuclease activity / DNA helicase activity / telomere maintenance / replication fork / determination of adult lifespan / double-strand break repair via homologous recombination / base-excision repair / HDR through Homologous Recombination (HRR) / G2/M DNA damage checkpoint / cellular response to gamma radiation / cellular senescence / double-strand break repair / chromosome / manganese ion binding / Processing of DNA double-strand break ends / Regulation of TP53 Activity through Phosphorylation / response to oxidative stress / DNA replication / chromosome, telomeric region / Hydrolases; Acting on ester bonds / nuclear speck / centrosome / DNA damage response / chromatin binding / protein-containing complex binding / nucleolus / magnesium ion binding / protein homodimerization activity / ATP hydrolysis activity / DNA binding / nucleoplasm / ATP binding / nucleus / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å | ||||||
Authors | Scheufler, C. / Villard, F. | ||||||
Funding support | 1items
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Citation | Journal: Nature / Year: 2024 Title: Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers. Authors: Ferretti, S. / Hamon, J. / de Kanter, R. / Scheufler, C. / Andraos-Rey, R. / Barbe, S. / Bechter, E. / Blank, J. / Bordas, V. / Dammassa, E. / Decker, A. / Di Nanni, N. / Dourdoigne, M. / ...Authors: Ferretti, S. / Hamon, J. / de Kanter, R. / Scheufler, C. / Andraos-Rey, R. / Barbe, S. / Bechter, E. / Blank, J. / Bordas, V. / Dammassa, E. / Decker, A. / Di Nanni, N. / Dourdoigne, M. / Gavioli, E. / Hattenberger, M. / Heuser, A. / Hemmerlin, C. / Hinrichs, J. / Kerr, G. / Laborde, L. / Jaco, I. / Nunez, E.J. / Martus, H.J. / Quadt, C. / Reschke, M. / Romanet, V. / Schaeffer, F. / Schoepfer, J. / Schrapp, M. / Strang, R. / Voshol, H. / Wartmann, M. / Welly, S. / Zecri, F. / Hofmann, F. / Mobitz, H. / Cortes-Cros, M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8pfp.cif.gz | 178.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8pfp.ent.gz | 136.2 KB | Display | PDB format |
PDBx/mmJSON format | 8pfp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pf/8pfp ftp://data.pdbj.org/pub/pdb/validation_reports/pf/8pfp | HTTPS FTP |
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-Related structure data
Related structure data | 8pflC 8pfoC C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 48740.156 Da / Num. of mol.: 1 / Mutation: E625A, R716A, K804A, E886A, R942A Source method: isolated from a genetically manipulated source Details: WRN helicase domain with 5 surface mutations. / Source: (gene. exp.) Homo sapiens (human) / Gene: WRN, RECQ3, RECQL2 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q14191, Hydrolases; Acting on ester bonds, DNA helicase |
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#2: Chemical | ChemComp-ZN / |
#3: Chemical | ChemComp-AGS / |
#4: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.09 Å3/Da / Density % sol: 41.04 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 20 % PEG3350 0.2 M Sodium citrate tribasic dihydrate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 22, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.58→40 Å / Num. obs: 50497 / % possible obs: 93.4 % / Redundancy: 1.8 % / CC1/2: 0.999 / Net I/σ(I): 12.8 |
Reflection shell | Resolution: 1.58→1.62 Å / Mean I/σ(I) obs: 1.14 / Num. unique obs: 3742 / CC1/2: 0.561 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.6→26.64 Å / Cor.coef. Fo:Fc: 0.958 / Cor.coef. Fo:Fc free: 0.952 / SU R Cruickshank DPI: 0.107 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.107 / SU Rfree Blow DPI: 0.102 / SU Rfree Cruickshank DPI: 0.103
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Displacement parameters | Biso mean: 32.55 Å2
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Refine analyze | Luzzati coordinate error obs: 0.24 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.6→26.64 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.6→1.61 Å
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Refinement TLS params. | Method: refined / Origin x: -16.1238 Å / Origin y: 3.4805 Å / Origin z: 11.2275 Å
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Refinement TLS group |
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