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Yorodumi- PDB-4ylj: Crystal structure of DYRK1A in complex with 10-Iodo-substituted 1... -
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-Basic information
Entry | Database: PDB / ID: 4ylj | ||||||
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Title | Crystal structure of DYRK1A in complex with 10-Iodo-substituted 11H-indolo[3,2-c]quinoline-6-carboxylic acid inhibitor 5j | ||||||
Components | Dual specificity tyrosine-phosphorylation-regulated kinase 1A | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / halogen / inhibitor / Structural Genomics / Structural Genomics Consortium / SGC / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
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 mRNA splicing, via spliceosome / 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 mRNA splicing, via spliceosome / amyloid-beta formation / negative regulation of DNA damage response, signal transduction by p53 class mediator / 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 / peptidyl-tyrosine phosphorylation / circadian rhythm / 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 / protein phosphorylation / axon / 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: 2.58 Å | ||||||
Authors | Chaikuad, A. / Falke, H. / Nowak, R. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Kunick, C. / Knapp, S. / Structural Genomics Consortium (SGC) | ||||||
Citation | Journal: J.Med.Chem. / Year: 2015 Title: 10-Iodo-11H-indolo[3,2-c]quinoline-6-carboxylic Acids Are Selective Inhibitors of DYRK1A. Authors: Falke, H. / Chaikuad, A. / Becker, A. / Loaec, N. / Lozach, O. / Abu Jhaisha, S. / Becker, W. / Jones, P.G. / Preu, L. / Baumann, K. / Knapp, S. / Meijer, L. / Kunick, C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4ylj.cif.gz | 593.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4ylj.ent.gz | 496.1 KB | Display | PDB format |
PDBx/mmJSON format | 4ylj.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4ylj_validation.pdf.gz | 2.9 MB | Display | wwPDB validaton report |
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Full document | 4ylj_full_validation.pdf.gz | 2.9 MB | Display | |
Data in XML | 4ylj_validation.xml.gz | 55.4 KB | Display | |
Data in CIF | 4ylj_validation.cif.gz | 73.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yl/4ylj ftp://data.pdbj.org/pub/pdb/validation_reports/yl/4ylj | HTTPS FTP |
-Related structure data
Related structure data | 4ylkC 4yllC 2wo6S C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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Unit cell |
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Components on special symmetry positions |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: _ / End auth comp-ID: LYS / End label comp-ID: LYS / Refine code: _
NCS ensembles :
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-Components
#1: Protein | Mass: 42081.535 Da / Num. of mol.: 4 / Fragment: UNP residues 127-485 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DYRK1A, DYRK, MNB, MNBH / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3)-R3-pRARE2 / References: UniProt: Q13627, dual-specificity kinase #2: Chemical | ChemComp-PG4 / #3: Chemical | ChemComp-SO4 / #4: Chemical | ChemComp-4E1 / #5: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
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-Sample preparation
Crystal | Density Matthews: 3.27 Å3/Da / Density % sol: 62.43 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8.8 Details: 37% PEG400, 0.2 M lithium sulfate, 0.1 M Tris, pH 8.8 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.92 Å |
Detector | Type: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Oct 31, 2013 |
Radiation | Monochromator: Si (111) double crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.92 Å / Relative weight: 1 |
Reflection | Resolution: 2.58→48.41 Å / Num. obs: 68848 / % possible obs: 99.6 % / Redundancy: 6.5 % / Biso Wilson estimate: 56.1 Å2 / Rmerge(I) obs: 0.066 / Net I/σ(I): 16.6 |
Reflection shell | Resolution: 2.58→2.72 Å / Redundancy: 6.6 % / Rmerge(I) obs: 0.884 / Mean I/σ(I) obs: 2.2 / % possible all: 99.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 2WO6 Resolution: 2.58→48.41 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.949 / SU B: 21.661 / SU ML: 0.223 / Cross valid method: THROUGHOUT / ESU R: 0.419 / ESU R Free: 0.25 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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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: 78.835 Å2
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Refine analyze | Luzzati coordinate error obs: 0.396 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Resolution: 2.58→48.41 Å
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Refine LS restraints |
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