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Yorodumi- PDB-6npu: C-abl Kinase domain with the activator(cmpd29), N-(1-(3,4-dichlor... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6npu | ||||||
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Title | C-abl Kinase domain with the activator(cmpd29), N-(1-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)acetamide | ||||||
Components | Tyrosine-protein kinase ABL1 | ||||||
Keywords | TRANSFERASE / activator / kinase / allosteric / SIGNALING PROTEIN | ||||||
Function / homology | Function and homology information : / positive regulation of actin filament binding / positive regulation of oxidoreductase activity / protein localization to cytoplasmic microtubule plus-end / DNA conformation change / podocyte apoptotic process / DN4 thymocyte differentiation / Role of ABL in ROBO-SLIT signaling / response to epinephrine / transitional one stage B cell differentiation ...: / positive regulation of actin filament binding / positive regulation of oxidoreductase activity / protein localization to cytoplasmic microtubule plus-end / DNA conformation change / podocyte apoptotic process / DN4 thymocyte differentiation / Role of ABL in ROBO-SLIT signaling / response to epinephrine / transitional one stage B cell differentiation / activation of protein kinase C activity / nicotinate-nucleotide adenylyltransferase activity / regulation of modification of synaptic structure / positive regulation of microtubule binding / delta-catenin binding / B cell proliferation involved in immune response / positive regulation of extracellular matrix organization / neuroepithelial cell differentiation / microspike assembly / positive regulation of Wnt signaling pathway, planar cell polarity pathway / cerebellum morphogenesis / positive regulation of blood vessel branching / B-1 B cell homeostasis / mitochondrial depolarization / neuropilin signaling pathway / negative regulation of ubiquitin-protein transferase activity / neuropilin binding / bubble DNA binding / negative regulation of protein serine/threonine kinase activity / activated T cell proliferation / cellular response to dopamine / regulation of cell motility / regulation of Cdc42 protein signal transduction / proline-rich region binding / positive regulation of dendrite development / mitogen-activated protein kinase binding / myoblast proliferation / syntaxin binding / regulation of hematopoietic stem cell differentiation / alpha-beta T cell differentiation / cardiac muscle cell proliferation / regulation of T cell differentiation / regulation of axon extension / HDR through Single Strand Annealing (SSA) / positive regulation of cell migration involved in sprouting angiogenesis / negative regulation of cell-cell adhesion / Fc-gamma receptor signaling pathway involved in phagocytosis / Myogenesis / positive regulation of osteoblast proliferation / regulation of microtubule polymerization / RUNX2 regulates osteoblast differentiation / platelet-derived growth factor receptor-beta signaling pathway / negative regulation of cellular senescence / positive regulation of focal adhesion assembly / associative learning / Bergmann glial cell differentiation / regulation of endocytosis / neuromuscular process controlling balance / negative regulation of mitotic cell cycle / actin monomer binding / negative regulation of BMP signaling pathway / negative regulation of long-term synaptic potentiation / endothelial cell migration / RHO GTPases Activate WASPs and WAVEs / positive regulation of T cell migration / signal transduction in response to DNA damage / BMP signaling pathway / negative regulation of double-strand break repair via homologous recombination / regulation of cell adhesion / mismatch repair / negative regulation of endothelial cell apoptotic process / canonical NF-kappaB signal transduction / four-way junction DNA binding / peptidyl-tyrosine autophosphorylation / positive regulation of substrate adhesion-dependent cell spreading / positive regulation of vasoconstriction / spleen development / positive regulation of stress fiber assembly / cellular response to transforming growth factor beta stimulus / ruffle / positive regulation of establishment of T cell polarity / ERK1 and ERK2 cascade / positive regulation of interleukin-2 production / ephrin receptor binding / actin filament polymerization / phosphotyrosine residue binding / positive regulation of endothelial cell migration / response to endoplasmic reticulum stress / positive regulation of mitotic cell cycle / substrate adhesion-dependent cell spreading / SH2 domain binding / positive regulation of release of sequestered calcium ion into cytosol / post-embryonic development / thymus development / regulation of autophagy / neural tube closure / establishment of localization in cell / integrin-mediated signaling pathway / regulation of actin cytoskeleton organization / protein kinase C binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.33 Å | ||||||
Authors | Campobasso, N. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2019 Title: Identification and Optimization of Novel Small c-Abl Kinase Activators Using Fragment and HTS Methodologies. Authors: Simpson, G.L. / Bertrand, S.M. / Borthwick, J.A. / Campobasso, N. / Chabanet, J. / Chen, S. / Coggins, J. / Cottom, J. / Christensen, S.B. / Dawson, H.C. / Evans, H.L. / Hobbs, A.N. / Hong, ...Authors: Simpson, G.L. / Bertrand, S.M. / Borthwick, J.A. / Campobasso, N. / Chabanet, J. / Chen, S. / Coggins, J. / Cottom, J. / Christensen, S.B. / Dawson, H.C. / Evans, H.L. / Hobbs, A.N. / Hong, X. / Mangatt, B. / Munoz-Muriedas, J. / Oliff, A. / Qin, D. / Scott-Stevens, P. / Ward, P. / Washio, Y. / Yang, J. / Young, R.J. #1: Journal: Chem. Biol. / Year: 2011 Title: Discovery and characterization of a cell-permeable, small-molecule c-Abl kinase activator that binds to the myristoyl binding site. Authors: Yang, J. / Campobasso, N. / Biju, M.P. / Fisher, K. / Pan, X.Q. / Cottom, J. / Galbraith, S. / Ho, T. / Zhang, H. / Hong, X. / Ward, P. / Hofmann, G. / Siegfried, B. / Zappacosta, F. / ...Authors: Yang, J. / Campobasso, N. / Biju, M.P. / Fisher, K. / Pan, X.Q. / Cottom, J. / Galbraith, S. / Ho, T. / Zhang, H. / Hong, X. / Ward, P. / Hofmann, G. / Siegfried, B. / Zappacosta, F. / Washio, Y. / Cao, P. / Qu, J. / Bertrand, S. / Wang, D.Y. / Head, M.S. / Li, H. / Moores, S. / Lai, Z. / Johanson, K. / Burton, G. / Erickson-Miller, C. / Simpson, G. / Tummino, P. / Copeland, R.A. / Oliff, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6npu.cif.gz | 153.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6npu.ent.gz | 96.1 KB | Display | PDB format |
PDBx/mmJSON format | 6npu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/np/6npu ftp://data.pdbj.org/pub/pdb/validation_reports/np/6npu | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 34708.566 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ABL1, ABL, JTK7 Production host: Spodoptera aff. frugiperda 2 RZ-2014 (butterflies/moths) References: UniProt: P00519, non-specific protein-tyrosine kinase |
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-Non-polymers , 6 types, 80 molecules
#2: Chemical | #3: Chemical | #4: Chemical | ChemComp-SO4 / | #5: Chemical | #6: Chemical | ChemComp-2PE / | #7: Water | ChemComp-HOH / | |
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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: 2.99 Å3/Da / Density % sol: 58.84 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion Details: 1 - 3 % PEG 400 2M AmSO4 0.1 HEPES pH 7.5 cryo: 20% Glycerol |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 0.9787 Å |
Detector | Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Dec 3, 2008 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9787 Å / Relative weight: 1 |
Reflection | Resolution: 2.33→73.7 Å / Num. obs: 34988 / % possible obs: 95.9 % / Redundancy: 5.5 % / Biso Wilson estimate: 29.91 Å2 / Net I/σ(I): 10.9 |
Reflection shell | Resolution: 2.33→2.41 Å |
-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.33→73.7 Å / SU ML: 0.2591 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 22.6842
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 34.84 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.33→73.7 Å
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Refine LS restraints |
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LS refinement shell |
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