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Yorodumi- PDB-5ngr: Crystal structure of human MTH1 in complex with fragment inhibito... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5ngr | ||||||||||||||||||||||||||||||||||||||||||
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Title | Crystal structure of human MTH1 in complex with fragment inhibitor 8-(methylsulfanyl)-7H-purin-6-amine | ||||||||||||||||||||||||||||||||||||||||||
Components | 7,8-dihydro-8-oxoguanine triphosphatase | ||||||||||||||||||||||||||||||||||||||||||
Keywords | HYDROLASE / Inhibitor / Fragment / Oxidised nucleotides | ||||||||||||||||||||||||||||||||||||||||||
Function / homology | Function and homology information 2-hydroxy-ATP hydrolase activity / 2-hydroxy-dATP hydrolase activity / N6-methyl-(d)ATP hydrolase activity / O6-methyl-dGTP hydrolase activity / 2-hydroxy-dATP diphosphatase / dATP diphosphatase activity / ATP diphosphatase activity / 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity / 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity / hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides ...2-hydroxy-ATP hydrolase activity / 2-hydroxy-dATP hydrolase activity / N6-methyl-(d)ATP hydrolase activity / O6-methyl-dGTP hydrolase activity / 2-hydroxy-dATP diphosphatase / dATP diphosphatase activity / ATP diphosphatase activity / 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity / 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity / hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides / DNA protection / Phosphate bond hydrolysis by NUDT proteins / purine nucleoside catabolic process / snoRNA binding / Hydrolases; Acting on acid anhydrides; In phosphorus-containing anhydrides / response to cadmium ion / acrosomal vesicle / male gonad development / nuclear membrane / response to oxidative stress / mitochondrial matrix / DNA repair / mitochondrion / extracellular space / metal ion binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||||||||||||||||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||||||||||||||||||||||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å | ||||||||||||||||||||||||||||||||||||||||||
Authors | Gustafsson, R. / Rudling, A. / Almlof, I. / Homan, E. / Scobie, M. / Warpman Berglund, U. / Helleday, T. / Carlsson, J. / Stenmark, P. | ||||||||||||||||||||||||||||||||||||||||||
Funding support | Sweden, 13items
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Citation | Journal: J. Med. Chem. / Year: 2017 Title: Fragment-Based Discovery and Optimization of Enzyme Inhibitors by Docking of Commercial Chemical Space. Authors: Rudling, A. / Gustafsson, R. / Almlof, I. / Homan, E. / Scobie, M. / Warpman Berglund, U. / Helleday, T. / Stenmark, P. / Carlsson, J. | ||||||||||||||||||||||||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5ngr.cif.gz | 79.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5ngr.ent.gz | 58.2 KB | Display | PDB format |
PDBx/mmJSON format | 5ngr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ng/5ngr ftp://data.pdbj.org/pub/pdb/validation_reports/ng/5ngr | HTTPS FTP |
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-Related structure data
Related structure data | 5ngsC 5ngtC 3zr1S C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 0 / Ens-ID: 1 / Beg auth comp-ID: ALA / Beg label comp-ID: ALA / End auth comp-ID: VAL / End label comp-ID: VAL / Refine code: 0 / Auth seq-ID: 3 - 156 / Label seq-ID: 6 - 159
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-Components
#1: Protein | Mass: 18253.736 Da / Num. of mol.: 2 / Fragment: UNP Residues 42-197 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NUDT1, MTH1 / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: P36639, 8-oxo-dGTP diphosphatase, 2-hydroxy-dATP diphosphatase #2: Chemical | #3: Chemical | ChemComp-SO4 / #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: 2.29 Å3/Da / Density % sol: 46.19 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 5 mmol/L compound and 6 mmol/L MgCl2 were added to MTH1. Sitting drop vapor diffusion experiments at 293K were performed, and MTH1 (9.34 mg/mL) was mixed with reservoir solution (30% (w/v) ...Details: 5 mmol/L compound and 6 mmol/L MgCl2 were added to MTH1. Sitting drop vapor diffusion experiments at 293K were performed, and MTH1 (9.34 mg/mL) was mixed with reservoir solution (30% (w/v) PEG6000, 0.1 mol/L Sodium Acetate pH 3.7 and 0.2 mol/L LiSO4 in a 1:1 ratio. |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID23-2 / Wavelength: 0.8726 Å |
Detector | Type: DECTRIS PILATUS3 2M / Detector: PIXEL / Date: Dec 7, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.8726 Å / Relative weight: 1 |
Reflection | Resolution: 2.2→48.4 Å / Num. obs: 17597 / % possible obs: 99.9 % / Redundancy: 6.3 % / CC1/2: 0.991 / Rmerge(I) obs: 0.234 / Net I/σ(I): 8.1 |
Reflection shell | Resolution: 2.2→2.27 Å / Redundancy: 6.5 % / Rmerge(I) obs: 2.007 / Mean I/σ(I) obs: 2 / Num. unique obs: 1502 / CC1/2: 0.545 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3ZR1 Resolution: 2.2→48.4 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.919 / SU B: 8.104 / SU ML: 0.196 / Cross valid method: THROUGHOUT / ESU R: 0.311 / ESU R Free: 0.227 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 36.83 Å2
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Refinement step | Cycle: 1 / Resolution: 2.2→48.4 Å
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