+Open data
-Basic information
Entry | Database: PDB / ID: 7ajy | ||||||
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Title | Structure of DYRK1A in complex with compound 51 | ||||||
Components | Dual specificity tyrosine-phosphorylation-regulated kinase 1A | ||||||
Keywords | TRANSFERASE / SERINE/THREONINE-PROTEIN KINASE / PHOSPHOPROTEIN / KINASE SELECTIVITY / SBDD / SMALL MOLECULE 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 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 / molecular replacement / Resolution: 2.2 Å | ||||||
Authors | Dokurno, P. / Surgenor, A.E. / Kotschy, A. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2021 Title: Structure-Guided Discovery of Potent and Selective DYRK1A Inhibitors. Authors: Weber, C. / Sipos, M. / Paczal, A. / Balint, B. / Kun, V. / Foloppe, N. / Dokurno, P. / Massey, A.J. / Walmsley, D.L. / Hubbard, R.E. / Murray, J. / Benwell, K. / Edmonds, T. / Demarles, D. ...Authors: Weber, C. / Sipos, M. / Paczal, A. / Balint, B. / Kun, V. / Foloppe, N. / Dokurno, P. / Massey, A.J. / Walmsley, D.L. / Hubbard, R.E. / Murray, J. / Benwell, K. / Edmonds, T. / Demarles, D. / Bruno, A. / Burbridge, M. / Cruzalegui, F. / Kotschy, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7ajy.cif.gz | 156.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ajy.ent.gz | 119.7 KB | Display | PDB format |
PDBx/mmJSON format | 7ajy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7ajy_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7ajy_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 7ajy_validation.xml.gz | 28.1 KB | Display | |
Data in CIF | 7ajy_validation.cif.gz | 39.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/aj/7ajy ftp://data.pdbj.org/pub/pdb/validation_reports/aj/7ajy | HTTPS FTP |
-Related structure data
Related structure data | 7aj2C 7aj4C 7aj5C 7aj7C 7aj8C 7ajaC 7ajmC 7ajsC 7ajvC 7ajwC 7ak2C 7akaC 7akbC 7akeC 7akfC 7akhC 7aklC 2vx3S 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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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 41647.129 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DYRK1A, DYRK, MNB, MNBH / Cell line (production host): pLysS / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q13627, dual-specificity kinase #2: Chemical | #3: Chemical | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | Has protein modification | 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: 2.4 Å3/Da / Density % sol: 48.85 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5 Details: 30% PegMME 5k, 0.1M ammonium sulphate, 0.1M ADA buffer pH 6.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 11, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.14→46.5 Å / Num. obs: 40920 / % possible obs: 94.5 % / Redundancy: 2.8 % / Rmerge(I) obs: 0.072 / Net I/σ(I): 8.9 |
Reflection shell | Resolution: 2.14→2.26 Å / Redundancy: 2.7 % / Rmerge(I) obs: 0.481 / Mean I/σ(I) obs: 2.3 / Num. unique obs: 5085 / % possible all: 80.5 |
-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2vx3 Resolution: 2.2→25 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.932 / SU B: 6.43 / SU ML: 0.155 / SU R Cruickshank DPI: 0.262 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.262 / ESU R Free: 0.2 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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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: 104.54 Å2 / Biso mean: 33.603 Å2 / Biso min: 17.33 Å2
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Refinement step | Cycle: final / Resolution: 2.2→25 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.2→2.318 Å / Rfactor Rfree error: 0 / Total num. of bins used: 10
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