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Yorodumi- PDB-6fmd: Targeting myeloid differentiation using potent human dihydroorota... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6fmd | ||||||
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Title | Targeting myeloid differentiation using potent human dihydroorotate dehydrogenase (hDHODH) inhibitors based on 2-hydroxypyrazolo[1,5-a]pyridine scaffold | ||||||
Components | Dihydroorotate dehydrogenase (quinone), mitochondrialDihydroorotate dehydrogenase (quinone) | ||||||
Keywords | OXIDOREDUCTASE / DHODH / inhibitor complex | ||||||
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: 1.58 Å | ||||||
Authors | Goyal, P. / Jarva, M. / Andersson, M. / Lolli, M.L. / Friemann, R. | ||||||
Funding support | Sweden, 1items
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Citation | Journal: J. Med. Chem. / Year: 2018 Title: Targeting Myeloid Differentiation Using Potent 2-Hydroxypyrazolo[1,5- a]pyridine Scaffold-Based Human Dihydroorotate Dehydrogenase Inhibitors. Authors: Sainas, S. / Pippione, A.C. / Lupino, E. / Giorgis, M. / Circosta, P. / Gaidano, V. / Goyal, P. / Bonanni, D. / Rolando, B. / Cignetti, A. / Ducime, A. / Andersson, M. / Jarva, M. / ...Authors: Sainas, S. / Pippione, A.C. / Lupino, E. / Giorgis, M. / Circosta, P. / Gaidano, V. / Goyal, P. / Bonanni, D. / Rolando, B. / Cignetti, A. / Ducime, A. / Andersson, M. / Jarva, M. / Friemann, R. / Piccinini, M. / Ramondetti, C. / Buccinna, B. / Al-Karadaghi, S. / Boschi, D. / Saglio, G. / 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 | 6fmd.cif.gz | 172.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6fmd.ent.gz | 133.3 KB | Display | PDB format |
PDBx/mmJSON format | 6fmd.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fm/6fmd ftp://data.pdbj.org/pub/pdb/validation_reports/fm/6fmd | HTTPS FTP |
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-Related structure data
Related structure data | 5mutS 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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Unit cell |
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-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 42929.203 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DHODH / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: Q02127, dihydroorotate dehydrogenase (quinone) |
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-Non-polymers , 8 types, 176 molecules
#2: Chemical | ChemComp-DUH / | ||||||||||||
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#3: Chemical | #4: Chemical | ChemComp-FMN / | #5: Chemical | ChemComp-ACT / #6: Chemical | ChemComp-ORO / | #7: Chemical | ChemComp-GOL / #8: Chemical | ChemComp-PGE / #9: 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: 3.37 Å3/Da / Density % sol: 63.47 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.2 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: ID23-1 / Wavelength: 0.97242 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Apr 8, 2017 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97242 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.58→78.324 Å / Num. obs: 79465 / % possible obs: 99.6 % / Redundancy: 4.6 % / Rpim(I) all: 0.036 / Rrim(I) all: 0.08 / Rsym value: 0.071 / Net I/av σ(I): 8.6 / Net I/σ(I): 11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 5MUT Resolution: 1.58→78.32 Å / Cor.coef. Fo:Fc: 0.976 / Cor.coef. Fo:Fc free: 0.972 / SU B: 2.644 / SU ML: 0.039 / SU R Cruickshank DPI: 0.0567 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.057 / ESU R Free: 0.052 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.7 Å / Shrinkage radii: 0.7 Å / VDW probe radii: 1.3 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 109.19 Å2 / Biso mean: 26.408 Å2 / Biso min: 11.21 Å2
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Refinement step | Cycle: final / Resolution: 1.58→78.32 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.58→1.621 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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