+Open data
-Basic information
Entry | Database: PDB / ID: 7jww | ||||||
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Title | Crystal structure of human ALDH1A1 bound to compound (R)-28 | ||||||
Components | Retinal dehydrogenase 1 | ||||||
Keywords | CYTOSOLIC PROTEIN / Rossmann fold | ||||||
Function / homology | Function and homology information fructosamine catabolic process / 3-deoxyglucosone dehydrogenase activity / benzaldehyde dehydrogenase (NAD+) / benzaldehyde dehydrogenase (NAD+) activity / maintenance of lens transparency / gamma-aminobutyric acid biosynthetic process / retinal dehydrogenase / aminobutyraldehyde dehydrogenase / aminobutyraldehyde dehydrogenase (NAD+) activity / Fructose catabolism ...fructosamine catabolic process / 3-deoxyglucosone dehydrogenase activity / benzaldehyde dehydrogenase (NAD+) / benzaldehyde dehydrogenase (NAD+) activity / maintenance of lens transparency / gamma-aminobutyric acid biosynthetic process / retinal dehydrogenase / aminobutyraldehyde dehydrogenase / aminobutyraldehyde dehydrogenase (NAD+) activity / Fructose catabolism / Ethanol oxidation / cellular aldehyde metabolic process / RA biosynthesis pathway / glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity / aldehyde dehydrogenase (NAD+) / cellular detoxification of aldehyde / androgen binding / aldehyde dehydrogenase (NAD+) activity / retinal dehydrogenase activity / negative regulation of cold-induced thermogenesis / retinol metabolic process / retinoid metabolic process / GTPase activator activity / NAD binding / axon / synapse / extracellular exosome / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å | ||||||
Authors | Hurley, T.D. / Buchman, C. | ||||||
Funding support | United States, 1items
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Citation | Journal: Eur.J.Med.Chem. / Year: 2020 Title: Development of 2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one inhibitors of aldehyde dehydrogenase 1A (ALDH1A) as potential adjuncts to ovarian cancer chemotherapy. Authors: Huddle, B.C. / Grimley, E. / Chtcherbinine, M. / Buchman, C.D. / Takahashi, C. / Debnath, B. / McGonigal, S.C. / Mao, S. / Li, S. / Felton, J. / Pan, S. / Wen, B. / Sun, D. / Neamati, N. / ...Authors: Huddle, B.C. / Grimley, E. / Chtcherbinine, M. / Buchman, C.D. / Takahashi, C. / Debnath, B. / McGonigal, S.C. / Mao, S. / Li, S. / Felton, J. / Pan, S. / Wen, B. / Sun, D. / Neamati, N. / Buckanovich, R.J. / Hurley, T.D. / Larsen, S.D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7jww.cif.gz | 214.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7jww.ent.gz | 169 KB | Display | PDB format |
PDBx/mmJSON format | 7jww.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7jww_validation.pdf.gz | 763.4 KB | Display | wwPDB validaton report |
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Full document | 7jww_full_validation.pdf.gz | 767.2 KB | Display | |
Data in XML | 7jww_validation.xml.gz | 22.1 KB | Display | |
Data in CIF | 7jww_validation.cif.gz | 32.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jw/7jww ftp://data.pdbj.org/pub/pdb/validation_reports/jw/7jww | HTTPS FTP |
-Related structure data
Related structure data | 7jwsC 7jwtC 7jwuC 7jwvC 6dumS 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 on special symmetry positions |
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-Components
#1: Protein | Mass: 54897.590 Da / Num. of mol.: 1 / Mutation: N121S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ALDH1A1, ALDC, ALDH1, PUMB1 / Plasmid: pET7b / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: V9HW83, UniProt: P00352*PLUS |
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#2: Chemical | ChemComp-YB / |
#3: Chemical | ChemComp-VMG / |
#4: Chemical | ChemComp-CL / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.25 Å3/Da / Density % sol: 45.22 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.4 Details: 100 mM sodium BisTris, pH 6.4, 9% PEG3350, 200 mM NaCl, and 5-10 mM YbCl3, 250 uM 5-(4-(2-hydroxyethyl)phenyl)-1-methyl-6-((1-phenylethyl)thio)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, 1% v/v DMSO |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 19-BM / Wavelength: 0.98 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 210r / Detector: CCD / Date: Mar 20, 2018 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.6→50.01 Å / Num. obs: 66324 / % possible obs: 99.9 % / Redundancy: 9.6 % / Rmerge(I) obs: 0.089 / Rpim(I) all: 0.03 / Rrim(I) all: 0.094 / Χ2: 1.036 / Net I/av σ(I): 23.6 / Net I/σ(I): 9.8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6DUM Resolution: 1.6→50.01 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.922 / SU B: 6.919 / SU ML: 0.121 / SU R Cruickshank DPI: 0.1146 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.115 / ESU R Free: 0.114 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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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: 74.9 Å2 / Biso mean: 31.624 Å2 / Biso min: 2 Å2
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Refinement step | Cycle: final / Resolution: 1.6→50.01 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.6→1.642 Å / Rfactor Rfree error: 0
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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