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Yorodumi- PDB-5mut: Crystal structure of potent human Dihydroorotate Dehydrogenase in... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5mut | ||||||
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Title | Crystal structure of potent human Dihydroorotate Dehydrogenase inhibitors based on hydroxylated azole scaffolds | ||||||
Components | Dihydroorotate dehydrogenase (quinone), mitochondrial | ||||||
Keywords | OXIDOREDUCTASE / dhodh / human dhodh | ||||||
Function / homology | Function and homology information pyrimidine ribonucleotide biosynthetic process / dihydroorotate dehydrogenase (quinone) activity / dihydroorotate dehydrogenase (quinone) / dihydroorotate dehydrogenase activity / dihydroorotase activity / Pyrimidine biosynthesis / UDP biosynthetic process / 'de novo' UMP biosynthetic process / 'de novo' pyrimidine nucleobase biosynthetic process / mitochondrial inner membrane ...pyrimidine ribonucleotide biosynthetic process / dihydroorotate dehydrogenase (quinone) activity / dihydroorotate dehydrogenase (quinone) / dihydroorotate dehydrogenase activity / dihydroorotase activity / Pyrimidine biosynthesis / UDP biosynthetic process / 'de novo' UMP biosynthetic process / 'de novo' pyrimidine nucleobase biosynthetic process / mitochondrial inner membrane / mitochondrion / nucleoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.75 Å | ||||||
Authors | Goyal, P. / Andersson, M. / Moritzer, A.C. / Sainas, S. / Pippione, A.C. / Boschi, D. / Al-Kadaraghi, S. / Lolli, M. / Friemann, R. | ||||||
Citation | Journal: Eur J Med Chem / Year: 2017 Title: Design, synthesis, biological evaluation and X-ray structural studies of potent human dihydroorotate dehydrogenase inhibitors based on hydroxylated azole scaffolds. Authors: Sainas, S. / Pippione, A.C. / Giorgis, M. / Lupino, E. / Goyal, P. / Ramondetti, C. / Buccinna, B. / Piccinini, M. / Braga, R.C. / Andrade, C.H. / Andersson, M. / Moritzer, A.C. / Friemann, ...Authors: Sainas, S. / Pippione, A.C. / Giorgis, M. / Lupino, E. / Goyal, P. / Ramondetti, C. / Buccinna, B. / Piccinini, M. / Braga, R.C. / Andrade, C.H. / Andersson, M. / Moritzer, A.C. / Friemann, R. / Mensa, S. / Al-Kadaraghi, S. / Boschi, D. / Lolli, M.L. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5mut.cif.gz | 93.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5mut.ent.gz | 67.3 KB | Display | PDB format |
PDBx/mmJSON format | 5mut.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5mut_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 5mut_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 5mut_validation.xml.gz | 18.1 KB | Display | |
Data in CIF | 5mut_validation.cif.gz | 27.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mu/5mut ftp://data.pdbj.org/pub/pdb/validation_reports/mu/5mut | HTTPS FTP |
-Related structure data
Related structure data | 5mvcC 5mvdC 4ylwS 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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1 |
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Unit cell |
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-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 39654.266 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DHODH / Plasmid: pET-19b / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) References: UniProt: Q02127, dihydroorotate dehydrogenase (quinone) |
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-Non-polymers , 6 types, 309 molecules
#2: Chemical | ChemComp-FMN / | ||||
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#3: Chemical | ChemComp-ORO / | ||||
#4: Chemical | ChemComp-HYT / | ||||
#5: Chemical | #6: Chemical | #7: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.7 Å3/Da / Density % sol: 66.75 % / Mosaicity: 0.14 ° |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 5 Details: 0.2M KBr, 0.2M KSCN, 0.1M NaAc pH 5.2, 25% PEG 400, 2% PGA-LM |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID23-2 / Wavelength: 0.87 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Sep 23, 2016 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.87 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.75→78.878 Å / Num. obs: 59814 / % possible obs: 100 % / Redundancy: 18.5 % / Biso Wilson estimate: 11.12 Å2 / Rpim(I) all: 0.063 / Rrim(I) all: 0.275 / Rsym value: 0.268 / Net I/av σ(I): 2.6 / Net I/σ(I): 9 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4YLW Resolution: 1.75→26.807 Å / SU ML: 0.15 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 16.47
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 67.25 Å2 / Biso mean: 12.8739 Å2 / Biso min: 1.81 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.75→26.807 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 21 / % reflection obs: 100 %
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