+Open data
-Basic information
Entry | Database: PDB / ID: 7fhs | |||||||||||||||||||||||||||
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Title | Crystal structure of DYRK1A in complex with RD0392 | |||||||||||||||||||||||||||
Components | Dual specificity tyrosine-phosphorylation-regulated kinase 1A | |||||||||||||||||||||||||||
Keywords | TRANSFERASE / DYRK1A / Kinase / Inhibitor | |||||||||||||||||||||||||||
Function / homology | Function and homology information histone H3T45 kinase activity / positive regulation of protein deacetylation / peptidyl-serine autophosphorylation / negative regulation of DNA methylation-dependent heterochromatin formation / dual-specificity kinase / [RNA-polymerase]-subunit kinase / negative regulation of microtubule polymerization / tau-protein kinase activity / negative regulation of DNA damage response, signal transduction by p53 class mediator / amyloid-beta formation ...histone H3T45 kinase activity / positive regulation of protein deacetylation / peptidyl-serine autophosphorylation / negative regulation of DNA methylation-dependent heterochromatin formation / dual-specificity kinase / [RNA-polymerase]-subunit kinase / negative regulation of microtubule polymerization / tau-protein kinase activity / negative regulation of DNA damage response, signal transduction by p53 class mediator / amyloid-beta formation / negative regulation of mRNA splicing, via spliceosome / G0 and Early G1 / peptidyl-tyrosine autophosphorylation / cytoskeletal protein binding / protein serine/threonine/tyrosine kinase activity / tubulin binding / RNA polymerase II CTD heptapeptide repeat kinase activity / positive regulation of RNA splicing / peptidyl-threonine phosphorylation / non-membrane spanning protein tyrosine kinase activity / tau protein binding / circadian rhythm / peptidyl-tyrosine phosphorylation / : / nervous system development / actin binding / peptidyl-serine phosphorylation / protein tyrosine kinase activity / protein autophosphorylation / transcription coactivator activity / cytoskeleton / protein kinase activity / nuclear speck / ribonucleoprotein complex / axon / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / dendrite / positive regulation of DNA-templated transcription / nucleoplasm / ATP binding / identical protein binding / nucleus / cytoplasm Similarity search - Function | |||||||||||||||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.42 Å | |||||||||||||||||||||||||||
Authors | Kikuchi, M. / Sumida, T. / Hosoya, T. / Kii, I. / Umehara, T. | |||||||||||||||||||||||||||
Funding support | Japan, 8items
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Citation | Journal: Eur.J.Med.Chem. / Year: 2022 Title: Structure-activity relationship for the folding intermediate-selective inhibition of DYRK1A. Authors: Miyazaki, Y. / Kikuchi, M. / Umezawa, K. / Descamps, A. / Nakamura, D. / Furuie, G. / Sumida, T. / Saito, K. / Kimura, N. / Niwa, T. / Sumida, Y. / Umehara, T. / Hosoya, T. / Kii, I. | |||||||||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7fhs.cif.gz | 290.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7fhs.ent.gz | 234.5 KB | Display | PDB format |
PDBx/mmJSON format | 7fhs.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7fhs_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 7fhs_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 7fhs_validation.xml.gz | 52.6 KB | Display | |
Data in CIF | 7fhs_validation.cif.gz | 70.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fh/7fhs ftp://data.pdbj.org/pub/pdb/validation_reports/fh/7fhs | HTTPS FTP |
-Related structure data
Related structure data | 7fhtC 3anrS 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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2 |
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3 |
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4 |
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Unit cell |
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-Components
#1: Protein | Mass: 42007.391 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DYRK1A, DYRK, MNB, MNBH / Production host: Escherichia coli (E. coli) / References: UniProt: Q13627, dual-specificity kinase #2: Chemical | ChemComp-4VZ / ( #3: Chemical | ChemComp-GOL / #4: Water | ChemComp-HOH / | 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: 2.62 Å3/Da / Density % sol: 53.09 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 100 mM Bis-Tris propane (pH 8.0), 200 mM Sodium fluoride and 18 % (w/v) PEG 3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Photon Factory / Beamline: BL-17A / Wavelength: 0.98 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Apr 25, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 2.42→48.12 Å / Num. obs: 67838 / % possible obs: 99.5 % / Redundancy: 6.7 % / Rsym value: 0.15 / Net I/σ(I): 10.2 |
Reflection shell | Resolution: 2.42→2.48 Å / Num. unique obs: 4466 / Rsym value: 1.432 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3ANR Resolution: 2.42→45 Å / Cor.coef. Fo:Fc: 0.938 / Cor.coef. Fo:Fc free: 0.912 / SU B: 12.91 / SU ML: 0.274 / Cross valid method: THROUGHOUT / ESU R: 0.455 / ESU R Free: 0.287 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
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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 mean: 52.568 Å2
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Refinement step | Cycle: 1 / Resolution: 2.42→45 Å
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