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Yorodumi- PDB-6b5i: ALDH1A2 liganded with 1-(4-cyanophenyl)-N-(3-fluorophenyl)-3-[4-(... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6b5i | |||||||||
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Title | ALDH1A2 liganded with 1-(4-cyanophenyl)-N-(3-fluorophenyl)-3-[4-(methylsulfonyl)phenyl]-1H-pyrazole-4-carboxamide (compound CM121) | |||||||||
Components | Retinal dehydrogenase 2 | |||||||||
Keywords | OXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR / retinoic acid signaling / male contraception / drug discovery / drug development / OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR complex | |||||||||
Function / homology | Function and homology information determination of bilateral symmetry / retinoic acid receptor signaling pathway involved in somitogenesis / regulation of vascular endothelial cell proliferation / 9-cis-retinoic acid biosynthetic process / 3-chloroallyl aldehyde dehydrogenase activity / retinoic acid biosynthetic process / retinal dehydrogenase / ureter maturation / embryonic camera-type eye development / morphogenesis of embryonic epithelium ...determination of bilateral symmetry / retinoic acid receptor signaling pathway involved in somitogenesis / regulation of vascular endothelial cell proliferation / 9-cis-retinoic acid biosynthetic process / 3-chloroallyl aldehyde dehydrogenase activity / retinoic acid biosynthetic process / retinal dehydrogenase / ureter maturation / embryonic camera-type eye development / morphogenesis of embryonic epithelium / pituitary gland development / RA biosynthesis pathway / proximal/distal pattern formation / vitamin A metabolic process / neural crest cell development / retinal metabolic process / hindbrain development / embryonic digestive tract development / aldehyde dehydrogenase (NAD+) activity / cardiac muscle tissue development / retinal binding / response to vitamin A / embryonic forelimb morphogenesis / pancreas development / retinal dehydrogenase activity / neural tube development / retinol metabolic process / retinoic acid metabolic process / midgut development / blood vessel development / face development / heart morphogenesis / cellular response to retinoic acid / response to retinoic acid / liver development / kidney development / response to cytokine / lung development / neuron differentiation / response to estradiol / protein homotetramerization / cell population proliferation / positive regulation of apoptotic process / negative regulation of cell population proliferation / positive regulation of cell population proliferation / positive regulation of gene expression / perinuclear region of cytoplasm / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.6 Å | |||||||||
Authors | Chen, Y. / Zhu, J.-Y. / Schonbrunn, E. | |||||||||
Funding support | United States, 2items
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Citation | Journal: ACS Chem. Biol. / Year: 2018 Title: Structural Basis of ALDH1A2 Inhibition by Irreversible and Reversible Small Molecule Inhibitors. Authors: Chen, Y. / Zhu, J.Y. / Hong, K.H. / Mikles, D.C. / Georg, G.I. / Goldstein, A.S. / Amory, J.K. / Schonbrunn, E. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6b5i.cif.gz | 384.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6b5i.ent.gz | 314 KB | Display | PDB format |
PDBx/mmJSON format | 6b5i.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/b5/6b5i ftp://data.pdbj.org/pub/pdb/validation_reports/b5/6b5i | HTTPS FTP |
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-Related structure data
Related structure data | 6aljSC 6b5gC 6b5hC 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
#1: Protein | Mass: 54170.602 Da / Num. of mol.: 4 / Fragment: UNP residues 26-518 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ALDH1A2, RALDH2 / Plasmid: pET28 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21Star(DE3) / References: UniProt: O94788, retinal dehydrogenase #2: Chemical | ChemComp-CU4 / #3: 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: 2.23 Å3/Da / Density % sol: 44.74 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop Details: 40 mg/mL ALDH1A2, 0.2 M sodium citrate tribasic dehydrate, 25% w/v PEG3350, 1.3 mM CM121, 10% DMSO |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Aug 18, 2016 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Rosenbaum-Rock double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.6→81.535 Å / Num. obs: 59848 / % possible obs: 99.3 % / Observed criterion σ(I): -3 / Redundancy: 7.368 % / Biso Wilson estimate: 36.24 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.123 / Rrim(I) all: 0.133 / Χ2: 1.009 / Net I/σ(I): 14.62 / Num. measured all: 440966 / Scaling rejects: 103 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 6ALJ Resolution: 2.6→81.535 Å / SU ML: 0.34 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 33.43 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 89.97 Å2 / Biso mean: 45.2584 Å2 / Biso min: 14.81 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.6→81.535 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: 8
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