+Open data
-Basic information
Entry | Database: PDB / ID: 7akh | ||||||
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Title | Structure of DYRK2 in complex with compound 58 | ||||||
Components | Dual specificity tyrosine-phosphorylation-regulated kinase 2 | ||||||
Keywords | TRANSFERASE / SERINE/THREONINE-PROTEIN KINASE / PHOSPHOPROTEIN / KINASE SELECTIVITY / SBDD / SMALL MOLECULE INHIBITOR | ||||||
Function / homology | Function and homology information dual-specificity kinase / negative regulation of calcineurin-NFAT signaling cascade / smoothened signaling pathway / positive regulation of glycogen biosynthetic process / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / ubiquitin ligase complex / protein serine/threonine/tyrosine kinase activity / regulation of signal transduction by p53 class mediator / manganese ion binding / protein tyrosine kinase activity ...dual-specificity kinase / negative regulation of calcineurin-NFAT signaling cascade / smoothened signaling pathway / positive regulation of glycogen biosynthetic process / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / ubiquitin ligase complex / protein serine/threonine/tyrosine kinase activity / regulation of signal transduction by p53 class mediator / manganese ion binding / protein tyrosine kinase activity / Regulation of TP53 Activity through Phosphorylation / cytoskeleton / ribonucleoprotein complex / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / DNA damage response / magnesium ion binding / nucleoplasm / ATP binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.85 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 | 7akh.cif.gz | 98.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7akh.ent.gz | 71.9 KB | Display | PDB format |
PDBx/mmJSON format | 7akh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7akh_validation.pdf.gz | 783.3 KB | Display | wwPDB validaton report |
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Full document | 7akh_full_validation.pdf.gz | 792.3 KB | Display | |
Data in XML | 7akh_validation.xml.gz | 17.7 KB | Display | |
Data in CIF | 7akh_validation.cif.gz | 23.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ak/7akh ftp://data.pdbj.org/pub/pdb/validation_reports/ak/7akh | HTTPS FTP |
-Related structure data
Related structure data | 7aj2C 7aj4C 7aj5C 7aj7C 7aj8C 7ajaC 7ajmC 7ajsC 7ajvC 7ajwC 7ajyC 7ak2C 7akaC 7akbC 7akeC 7akfC 7aklC 3k2lS 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: 49600.906 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DYRK2 / Cell line (production host): pLysS / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q92630, dual-specificity kinase |
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#2: Chemical | ChemComp-RK8 / |
#3: Chemical | ChemComp-CL / |
#4: Water | ChemComp-HOH / |
Has ligand of interest | Y |
Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.68 Å3/Da / Density % sol: 54.17 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: 25% PEG 4k, 0.1M Tris buffer pH 8.5, 0.1M Li sulphate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9763 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jan 30, 2010 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9763 Å / Relative weight: 1 |
Reflection | Resolution: 2.81→84.2 Å / Num. obs: 13805 / % possible obs: 100 % / Redundancy: 6.9 % / Rmerge(I) obs: 0.097 / Net I/σ(I): 12.2 |
Reflection shell | Resolution: 2.81→2.88 Å / Redundancy: 7 % / Rmerge(I) obs: 0.874 / Mean I/σ(I) obs: 2.2 / Num. unique obs: 984 / % possible all: 99.9 |
-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3k2l Resolution: 2.85→20 Å / Cor.coef. Fo:Fc: 0.951 / Cor.coef. Fo:Fc free: 0.921 / SU B: 15.401 / SU ML: 0.289 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.361 / 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: 197.38 Å2 / Biso mean: 69.943 Å2 / Biso min: 40.94 Å2
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Refinement step | Cycle: final / Resolution: 2.85→20 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.85→3.001 Å / Rfactor Rfree error: 0 / Total num. of bins used: 10
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