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Yorodumi- PDB-7gqt: Crystal Structure of Werner helicase fragment 517-945 in complex ... -
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-Basic information
Entry | Database: PDB / ID: 7gqt | ||||||
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Title | Crystal Structure of Werner helicase fragment 517-945 in complex with ATP | ||||||
Components | Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN | ||||||
Keywords | HYDROLASE / HELICASE / WERNER SYNDROME / DNA REPAIR | ||||||
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) / 3'-5' DNA helicase activity / response to UV-C / Resolution of D-loop Structures through Holliday Junction Intermediates / exonuclease activity / DNA duplex unwinding / HDR through Single Strand Annealing (SSA) / DNA metabolic process / Impaired BRCA2 binding to RAD51 / DNA synthesis involved in DNA repair / DNA unwinding involved in DNA replication / replication fork processing / Presynaptic phase of homologous DNA pairing and strand exchange / replicative senescence / SUMOylation of DNA damage response and repair proteins / four-way junction DNA binding / 3'-5' exonuclease activity / DNA helicase activity / cellular response to starvation / telomere maintenance / replication fork / determination of adult lifespan / double-strand break repair via homologous recombination / base-excision repair / cellular response to gamma radiation / HDR through Homologous Recombination (HRR) / G2/M DNA damage checkpoint / double-strand break repair / cellular senescence / chromosome / manganese ion binding / Processing of DNA double-strand break ends / response to oxidative stress / Regulation of TP53 Activity through Phosphorylation / 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 / ATP hydrolysis activity / protein homodimerization activity / DNA binding / nucleoplasm / ATP binding / nucleus / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.21 Å | ||||||
Authors | Classen, M. / Benz, J. / Brugger, D. / Rudolph, M.G. | ||||||
Funding support | Switzerland, 1items
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Citation | Journal: Nature / Year: 2024 Title: Chemoproteomic discovery of a covalent allosteric inhibitor of WRN helicase. Authors: Baltgalvis, K.A. / Lamb, K.N. / Symons, K.T. / Wu, C.C. / Hoffman, M.A. / Snead, A.N. / Song, X. / Glaza, T. / Kikuchi, S. / Green, J.C. / Rogness, D.C. / Lam, B. / Rodriguez-Aguirre, M.E. / ...Authors: Baltgalvis, K.A. / Lamb, K.N. / Symons, K.T. / Wu, C.C. / Hoffman, M.A. / Snead, A.N. / Song, X. / Glaza, T. / Kikuchi, S. / Green, J.C. / Rogness, D.C. / Lam, B. / Rodriguez-Aguirre, M.E. / Woody, D.R. / Eissler, C.L. / Rodiles, S. / Negron, S.M. / Bernard, S.M. / Tran, E. / Pollock, J. / Tabatabaei, A. / Contreras, V. / Williams, H.N. / Pastuszka, M.K. / Sigler, J.J. / Pettazzoni, P. / Rudolph, M.G. / Classen, M. / Brugger, D. / Claiborne, C. / Plancher, J.M. / Cuartas, I. / Seoane, J. / Burgess, L.E. / Abraham, R.T. / Weinstein, D.S. / Simon, G.M. / Patricelli, M.P. / Kinsella, T.M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7gqt.cif.gz | 185.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7gqt.ent.gz | 144.8 KB | Display | PDB format |
PDBx/mmJSON format | 7gqt.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gq/7gqt ftp://data.pdbj.org/pub/pdb/validation_reports/gq/7gqt | HTTPS FTP |
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-Group deposition
ID | G_1002280 (4 entries) |
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Title | To be published |
Type | undefined |
Description | A set of wrn crystal structures |
-Related structure data
Similar structure data | Similarity search - Function & homologyF&H Search |
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-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 50064.746 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: WRN / Plasmid: pFastBac1_hWRN(517-945)_C-H3CV-GFP-10His / Cell line (production host): SF9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q14191 | ||||||||
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#2: Chemical | #3: Chemical | ChemComp-ATP / | #4: Chemical | ChemComp-MG / | #5: 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: 2.38 Å3/Da / Density % sol: 48.39 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 6.2 Details: 5 mg/mL protein in 20mM TRIS/HCl pH7.5, 350mM NaCl, 0.25mM TCEP, 2.5% glycerol mixed 20nL with 20nL seed solution and 110nL reservoir consisting of 0.2M NaCl, 0.1M Na/K Phosphate, 10%w/v PEG8000 |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.99997 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: PSI PILATUS 6M / Detector: PIXEL / Date: Sep 13, 2021 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.99997 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.21→52.66 Å / Num. obs: 23329 / % possible obs: 98.7 % / Redundancy: 6.866 % / Biso Wilson estimate: 28.12 Å2 / CC1/2: 0.988 / Rmerge(I) obs: 0.433 / Rrim(I) all: 0.469 / Χ2: 0.688 / Net I/σ(I): 4.99 / Num. measured all: 160168 / Scaling rejects: 114 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: inhouse model Resolution: 2.21→52.66 Å / SU ML: 0.36 / Cross valid method: THROUGHOUT / σ(F): 1.42 / Phase error: 29.17 / Stereochemistry target values: ML Details: gamma-phosphate has higher B-values than beta-phosphate, indicating that it might be a mixture of ADPATP.
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 140.84 Å2 / Biso mean: 41.5418 Å2 / Biso min: 16.46 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.21→52.66 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 5
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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