+Open data
-Basic information
Entry | Database: PDB / ID: 7akl | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of DYRK1A in complex with compound 50 | ||||||
Components | Dual specificity tyrosine-phosphorylation-regulated kinase 1ADYRK1A | ||||||
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 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 / protein serine/threonine/tyrosine kinase activity / cytoskeletal protein binding / 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: 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 |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 7akl.cif.gz | 90.1 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7akl.ent.gz | 64.6 KB | Display | PDB format |
PDBx/mmJSON format | 7akl.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ak/7akl ftp://data.pdbj.org/pub/pdb/validation_reports/ak/7akl | HTTPS FTP |
---|
-Related structure data
Related structure data | 7aj2C 7aj4C 7aj5C 7aj7C 7aj8C 7ajaC 7ajmC 7ajsC 7ajvC 7ajwC 7ajyC 7ak2C 7akaC 7akbC 7akeC 7akfC 7akhC 2vx3S C: citing same article (ref.) S: Starting model for refinement |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-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 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): pLysS / References: UniProt: Q13627, dual-specificity kinase |
---|---|
#2: Chemical | ChemComp-RK5 / |
#3: Chemical | ChemComp-CL / |
#4: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.5 Å3/Da / Density % sol: 50.75 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 6.5 / Details: 12% PEG3350, 0.1M MES buffer pH6.5, 0.2M MgCl2 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.9795 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Jul 14, 2010 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 1.95→29.1 Å / Num. obs: 31494 / % possible obs: 98.9 % / Redundancy: 7.2 % / Rmerge(I) obs: 0.152 / Net I/σ(I): 8.2 |
Reflection shell | Resolution: 1.95→2 Å / Redundancy: 7.2 % / Rmerge(I) obs: 0.714 / Mean I/σ(I) obs: 2.5 / Num. unique obs: 1 / % possible all: 97.4 |
-Phasing
Phasing | Method: molecular replacement |
---|
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2vx3 Resolution: 2→25 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.936 / WRfactor Rfree: 0.2116 / WRfactor Rwork: 0.1678 / FOM work R set: 0.8606 / SU B: 3.742 / SU ML: 0.102 / SU R Cruickshank DPI: 0.1486 / SU Rfree: 0.1411 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.149 / ESU R Free: 0.141 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 102.81 Å2 / Biso mean: 27.351 Å2 / Biso min: 12 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2→25 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 2→2.107 Å / Rfactor Rfree error: 0 / Total num. of bins used: 10
|