+Open data
-Basic information
Entry | Database: PDB / ID: 7a4s | ||||||
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Title | Structure of DYRK1A in complex with compound 2 | ||||||
Components | Dual specificity tyrosine-phosphorylation-regulated kinase 1A | ||||||
Keywords | TRANSFERASE / SERINE/THREONINE-PROTEIN KINASE / PHOSPHOPROTEIN / KINASE / SBDD / FBLD / 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 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 / molecular replacement / Resolution: 3.1 Å | ||||||
Authors | Dokurno, P. / Surgenor, A.E. / Hubbard, R.E. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2021 Title: Fragment-Derived Selective Inhibitors of Dual-Specificity Kinases DYRK1A and DYRK1B. Authors: Lee Walmsley, D. / Murray, J.B. / Dokurno, P. / Massey, A.J. / Benwell, K. / Fiumana, A. / Foloppe, N. / Ray, S. / Smith, J. / Surgenor, A.E. / Edmonds, T. / Demarles, D. / Burbridge, M. / ...Authors: Lee Walmsley, D. / Murray, J.B. / Dokurno, P. / Massey, A.J. / Benwell, K. / Fiumana, A. / Foloppe, N. / Ray, S. / Smith, J. / Surgenor, A.E. / Edmonds, T. / Demarles, D. / Burbridge, M. / Cruzalegui, F. / Kotschy, A. / Hubbard, R.E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7a4s.cif.gz | 85 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7a4s.ent.gz | 61 KB | Display | PDB format |
PDBx/mmJSON format | 7a4s.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7a4s_validation.pdf.gz | 529.8 KB | Display | wwPDB validaton report |
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Full document | 7a4s_full_validation.pdf.gz | 532.3 KB | Display | |
Data in XML | 7a4s_validation.xml.gz | 14.9 KB | Display | |
Data in CIF | 7a4s_validation.cif.gz | 19.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/a4/7a4s ftp://data.pdbj.org/pub/pdb/validation_reports/a4/7a4s | HTTPS FTP |
-Related structure data
Related structure data | 7a4oC 7a4rC 7a4wC 7a4zC 7a51C 7a52C 7a53C 7a55C 7a5bC 7a5dC 7a5lC 7a5nC 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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Unit cell |
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-Components
#1: Protein | Mass: 41647.129 Da / Num. of mol.: 1 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 |
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#2: Chemical | ChemComp-QYE / |
#3: 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: 2.8 Å3/Da / Density % sol: 56.1 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 6.5 / Details: 0.1M MES buffer at pH 6.5, 12% Peg3350, 0.2M MgCl2 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9793 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Sep 10, 2009 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9793 Å / Relative weight: 1 |
Reflection | Resolution: 3.1→50 Å / Num. obs: 8852 / % possible obs: 96.9 % / Redundancy: 6.1 % / Rmerge(I) obs: 0.139 / Net I/σ(I): 12.3 |
Reflection shell | Resolution: 3.1→3.21 Å / Rmerge(I) obs: 0.76 / Num. unique obs: 702 / % possible all: 79.1 |
-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: 3.1→20 Å / Cor.coef. Fo:Fc: 0.95 / Cor.coef. Fo:Fc free: 0.924 / SU B: 21.302 / SU ML: 0.349 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.442 / 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: 185.09 Å2 / Biso mean: 65.896 Å2 / Biso min: 18.3 Å2
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Refinement step | Cycle: final / Resolution: 3.1→20 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 3.1→3.263 Å / Rfactor Rfree error: 0 / Total num. of bins used: 10
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