+Open data
-Basic information
Entry | Database: PDB / ID: 8t2h | ||||||
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Title | DYRK1A complex with DYR530 | ||||||
Components | Dual specificity tyrosine-phosphorylation-regulated kinase 1ADYRK1A | ||||||
Keywords | LIGASE/LIGASE INHIBITOR / Kinase / Inhibitor / Alzheimer's Disease / LIGASE / LIGASE-LIGASE 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 DNA damage response, signal transduction by p53 class mediator / negative regulation of mRNA splicing, via spliceosome ...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 / negative regulation of mRNA splicing, via spliceosome / amyloid-beta formation / 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 / MOLECULAR REPLACEMENT / Resolution: 1.85 Å | ||||||
Authors | Montfort, W.R. / Basantes, L.E. | ||||||
Funding support | United States, 1items
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Citation | Journal: To Be Published Title: Discovery of DYR684, a Potent, Selective, Metabolically Stable, DYRK1A/B PROTAC utilizing a Novel Cereblon Molecular Glue Authors: Montfort, W.R. / Basantes, L.E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8t2h.cif.gz | 160.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8t2h.ent.gz | 125.1 KB | Display | PDB format |
PDBx/mmJSON format | 8t2h.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t2/8t2h ftp://data.pdbj.org/pub/pdb/validation_reports/t2/8t2h | HTTPS FTP |
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-Related structure data
Similar structure data | Similarity search - Function & homologyF&H Search |
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-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 42438.785 Da / Num. of mol.: 2 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, [RNA-polymerase]-subunit kinase, dual-specificity kinase #2: Chemical | Mass: 417.482 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: C23H24FN7 / Feature type: SUBJECT OF INVESTIGATION #3: Chemical | ChemComp-PG4 / | #4: Chemical | #5: 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: 2.27 Å3/Da / Density % sol: 45.86 % / Description: Rod |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 6 / Details: 1.8 M sodium malonate, 1.3% PEG 400 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: LIQUID ANODE / Type: BRUKER METALJET / Wavelength: 1.34 Å |
Detector | Type: Bruker PHOTON III / Detector: PIXEL / Date: May 23, 2023 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.34 Å / Relative weight: 1 |
Reflection | Resolution: 1.85→24.88 Å / Num. obs: 67138 / % possible obs: 100 % / Redundancy: 7 % / CC1/2: 0.996 / Rmerge(I) obs: 0.119 / Net I/σ(I): 10.7 |
Reflection shell | Resolution: 1.85→1.89 Å / Redundancy: 4.6 % / Rmerge(I) obs: 0.76 / Mean I/σ(I) obs: 2 / Num. unique obs: 18823 / CC1/2: 0.48 / Χ2: 0.96 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.85→24.88 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.938 / SU B: 7.706 / SU ML: 0.098 / Cross valid method: THROUGHOUT / ESU R: 0.249 / ESU R Free: 0.124 / 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: 21.451 Å2
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Refinement step | Cycle: 1 / Resolution: 1.85→24.88 Å
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