+Open data
-Basic information
Entry | Database: PDB / ID: 8dhh | ||||||
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Title | DHODH IN COMPLEX WITH LIGAND 29 | ||||||
Components | Dihydroorotate dehydrogenase (quinone), mitochondrialDihydroorotate dehydrogenase (quinone) | ||||||
Keywords | OXIDOREDUCTASE/INHIBITOR / DIHYDROOROTATE DEHYDROGENASE / DHODH / OXIDOREDUCTASE / INHIBITOR / OXIDOREDUCTASE-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 / Resolution: 2.02 Å | ||||||
Authors | Shaffer, P.L. | ||||||
Funding support | 1items
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Citation | Journal: J.Med.Chem. / Year: 2022 Title: N -Heterocyclic 3-Pyridyl Carboxamide Inhibitors of DHODH for the Treatment of Acute Myelogenous Leukemia. Authors: Cisar, J.S. / Pietsch, C. / DeRatt, L.G. / Jacoby, E. / Kazmi, F. / Keohane, C. / Legenski, K. / Matico, R. / Shaffer, P. / Simonnet, Y. / Tanner, A. / Wang, C.Y. / Wang, W. / Attar, R. / ...Authors: Cisar, J.S. / Pietsch, C. / DeRatt, L.G. / Jacoby, E. / Kazmi, F. / Keohane, C. / Legenski, K. / Matico, R. / Shaffer, P. / Simonnet, Y. / Tanner, A. / Wang, C.Y. / Wang, W. / Attar, R. / Edwards, J.P. / Kuduk, S.D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8dhh.cif.gz | 98.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8dhh.ent.gz | 70.6 KB | Display | PDB format |
PDBx/mmJSON format | 8dhh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dh/8dhh ftp://data.pdbj.org/pub/pdb/validation_reports/dh/8dhh | HTTPS FTP |
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-Related structure data
Related structure data | 8dhfC 8dhgC 1d3gS S: Starting model for refinement 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 on special symmetry positions |
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-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 39984.664 Da / Num. of mol.: 1 / Fragment: TRUNCATED Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DHODH / Production host: Escherichia coli (E. coli) References: UniProt: Q02127, dihydroorotate dehydrogenase (quinone) |
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-Non-polymers , 7 types, 292 molecules
#2: Chemical | ChemComp-FMN / | ||||||
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#3: Chemical | ChemComp-ORO / | ||||||
#4: Chemical | ChemComp-TMK / ( | ||||||
#5: Chemical | #6: Chemical | ChemComp-GOL / | #7: Chemical | ChemComp-SO4 / | #8: Water | ChemComp-HOH / | |
-Details
Has ligand of interest | Y |
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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: 3.61 Å3/Da / Density % sol: 65.92 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 4.8 Details: 0.10 M Sodium Acetate pH4.8, 2.30 M (NH4)2SO4, 30% Glycerol |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1.00002 Å |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Apr 18, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.00002 Å / Relative weight: 1 |
Reflection | Resolution: 2.02→79.48 Å / Num. obs: 39538 / % possible obs: 99.5 % / Redundancy: 8 % / Biso Wilson estimate: 38.636 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.068 / Rrim(I) all: 0.073 / Χ2: 1.038 / Net I/σ(I): 21.61 |
Reflection shell | Resolution: 2.02→2.27 Å / Redundancy: 8.1 % / Rmerge(I) obs: 0.499 / Mean I/σ(I) obs: 4.84 / Num. unique obs: 11503 / CC1/2: 0.954 / Rrim(I) all: 0.533 / % possible all: 99.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1D3G Resolution: 2.02→79.48 Å / Cor.coef. Fo:Fc: 0.956 / Cor.coef. Fo:Fc free: 0.95 / SU B: 3.757 / SU ML: 0.098 / SU R Cruickshank DPI: 0.1358 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.136 / ESU R Free: 0.128 / Stereochemistry target values: MAXIMUM LIKELIHOOD
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 138.16 Å2 / Biso mean: 39.505 Å2 / Biso min: 21.2 Å2
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Refinement step | Cycle: final / Resolution: 2.02→79.48 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.02→2.072 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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