+Open data
-Basic information
Entry | Database: PDB / ID: 7q8w | ||||||
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Title | Crystal structure of TTBK1 in complex with VNG1.35 (compound 23) | ||||||
Components | Tau-tubulin kinase 1 | ||||||
Keywords | TRANSFERASE / kinase / TTBK1 / tau tubulin kinase / kinase inhibitor / Structural Genomics / Structural Genomics Consortium / SGC | ||||||
Function / homology | Function and homology information positive regulation of cyclin-dependent protein kinase activity / positive regulation of astrocyte activation / positive regulation of microglial cell activation / positive regulation of cysteine-type endopeptidase activity / microtubule associated complex / positive regulation of protein polymerization / tau-protein kinase activity / substantia nigra development / negative regulation of protein binding / peptidyl-threonine phosphorylation ...positive regulation of cyclin-dependent protein kinase activity / positive regulation of astrocyte activation / positive regulation of microglial cell activation / positive regulation of cysteine-type endopeptidase activity / microtubule associated complex / positive regulation of protein polymerization / tau-protein kinase activity / substantia nigra development / negative regulation of protein binding / peptidyl-threonine phosphorylation / tau protein binding / peptidyl-tyrosine phosphorylation / peptidyl-serine phosphorylation / protein tyrosine kinase activity / learning or memory / non-specific serine/threonine protein kinase / protein phosphorylation / negative regulation of gene expression / protein serine kinase activity / protein serine/threonine kinase activity / neuronal cell body / positive regulation of gene expression / perinuclear region of cytoplasm / signal transduction / nucleoplasm / ATP binding / nucleus / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.02 Å | ||||||
Authors | Chaikuad, A. / Nozal, V. / Martinez, A. / Knapp, S. / Structural Genomics Consortium (SGC) | ||||||
Funding support | Switzerland, 1items
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Citation | Journal: J.Med.Chem. / Year: 2022 Title: TDP-43 Modulation by Tau-Tubulin Kinase 1 Inhibitors: A New Avenue for Future Amyotrophic Lateral Sclerosis Therapy. Authors: Nozal, V. / Martinez-Gonzalez, L. / Gomez-Almeria, M. / Gonzalo-Consuegra, C. / Santana, P. / Chaikuad, A. / Perez-Cuevas, E. / Knapp, S. / Lietha, D. / Ramirez, D. / Petralla, S. / Monti, B. ...Authors: Nozal, V. / Martinez-Gonzalez, L. / Gomez-Almeria, M. / Gonzalo-Consuegra, C. / Santana, P. / Chaikuad, A. / Perez-Cuevas, E. / Knapp, S. / Lietha, D. / Ramirez, D. / Petralla, S. / Monti, B. / Gil, C. / Martin-Requero, A. / Palomo, V. / de Lago, E. / Martinez, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7q8w.cif.gz | 137.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7q8w.ent.gz | 106.9 KB | Display | PDB format |
PDBx/mmJSON format | 7q8w.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7q8w_validation.pdf.gz | 715.6 KB | Display | wwPDB validaton report |
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Full document | 7q8w_full_validation.pdf.gz | 717.5 KB | Display | |
Data in XML | 7q8w_validation.xml.gz | 13.5 KB | Display | |
Data in CIF | 7q8w_validation.cif.gz | 18.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/q8/7q8w ftp://data.pdbj.org/pub/pdb/validation_reports/q8/7q8w | HTTPS FTP |
-Related structure data
Related structure data | 7q8vC 7q8yC 7q8zC 7q90C 7qhwC 7jxxS S: Starting model for refinement C: citing same article (ref.) |
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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: 35515.031 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TTBK1, BDTK, KIAA1855 / Plasmid: pSUMO-LIC / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): -R3-pRARE2 References: UniProt: Q5TCY1, non-specific serine/threonine protein kinase |
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#2: Chemical | ChemComp-9IO / ~{ |
#3: Chemical | ChemComp-PO4 / |
#4: Chemical | ChemComp-EDO / |
#5: 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: 2.31 Å3/Da / Density % sol: 46.71 % |
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Crystal grow | Temperature: 293.15 K / Method: vapor diffusion, sitting drop / pH: 7.5 / Details: 26% PEG 3350, 0.2M sodium acetate, 0.1M tris 7.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1.00002 Å | |||||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Jul 5, 2021 | |||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.00002 Å / Relative weight: 1 | |||||||||||||||||||||||||||
Reflection | Resolution: 2.02→47.97 Å / Num. obs: 21353 / % possible obs: 98.9 % / Redundancy: 6.3 % / CC1/2: 1 / Rmerge(I) obs: 0.036 / Rpim(I) all: 0.017 / Rrim(I) all: 0.043 / Net I/σ(I): 19.9 | |||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 7jxx Resolution: 2.02→47.97 Å / Cor.coef. Fo:Fc: 0.969 / Cor.coef. Fo:Fc free: 0.955 / SU B: 10.005 / SU ML: 0.132 / SU R Cruickshank DPI: 0.1825 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.182 / ESU R Free: 0.164 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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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: 124.72 Å2 / Biso mean: 52.724 Å2 / Biso min: 28.47 Å2
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Refinement step | Cycle: final / Resolution: 2.02→47.97 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.02→2.072 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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