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Yorodumi- PDB-6npe: C-abl Kinase domain with the activator(cmpd6), 2-cyano-N-(4-(3,4-... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6npe | ||||||
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Title | C-abl Kinase domain with the activator(cmpd6), 2-cyano-N-(4-(3,4-dichlorophenyl)thiazol-2-yl)acetamide | ||||||
Components | Tyrosine-protein kinase ABL1 | ||||||
Keywords | TRANSFERASE / activator / kinase / allosteric / SIGNALING PROTEIN | ||||||
Function / homology | Function and homology information negative regulation of phospholipase C activity / positive regulation of actin filament binding / positive regulation of oxidoreductase activity / transitional one stage B cell differentiation / 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 ...negative regulation of phospholipase C activity / positive regulation of actin filament binding / positive regulation of oxidoreductase activity / transitional one stage B cell differentiation / 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 / activation of protein kinase C activity / nicotinate-nucleotide adenylyltransferase activity / regulation of modification of synaptic structure / positive regulation of extracellular matrix organization / positive regulation of microtubule binding / delta-catenin binding / B cell proliferation involved in immune response / 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 / negative regulation of ubiquitin-protein transferase activity / neuropilin signaling pathway / neuropilin binding / bubble DNA binding / regulation of Cdc42 protein signal transduction / negative regulation of protein serine/threonine kinase activity / activated T cell proliferation / cellular response to dopamine / regulation of cell motility / regulation of axon extension / proline-rich region binding / positive regulation of dendrite development / mitogen-activated protein kinase binding / myoblast proliferation / alpha-beta T cell differentiation / regulation of hematopoietic stem cell differentiation / syntaxin binding / cardiac muscle cell proliferation / HDR through Single Strand Annealing (SSA) / regulation of T cell differentiation / negative regulation of double-strand break repair via homologous recombination / positive regulation of cell migration involved in sprouting angiogenesis / Fc-gamma receptor signaling pathway involved in phagocytosis / negative regulation of cell-cell adhesion / Myogenesis / regulation of microtubule polymerization / positive regulation of osteoblast proliferation / RUNX2 regulates osteoblast differentiation / platelet-derived growth factor receptor-beta signaling pathway / positive regulation of focal adhesion assembly / negative regulation of cellular senescence / negative regulation of long-term synaptic potentiation / Bergmann glial cell differentiation / associative learning / neuromuscular process controlling balance / regulation of endocytosis / actin monomer binding / negative regulation of BMP signaling pathway / negative regulation of mitotic cell cycle / mismatch repair / endothelial cell migration / RHO GTPases Activate WASPs and WAVEs / positive regulation of T cell migration / canonical NF-kappaB signal transduction / BMP signaling pathway / negative regulation of endothelial cell apoptotic process / regulation of cell adhesion / positive regulation of substrate adhesion-dependent cell spreading / four-way junction DNA binding / signal transduction in response to DNA damage / peptidyl-tyrosine autophosphorylation / positive regulation of vasoconstriction / spleen development / positive regulation of stress fiber assembly / ruffle / ERK1 and ERK2 cascade / cellular response to transforming growth factor beta stimulus / positive regulation of establishment of T cell polarity / positive regulation of interleukin-2 production / actin filament polymerization / SH2 domain binding / response to endoplasmic reticulum stress / phosphotyrosine residue binding / ephrin receptor binding / positive regulation of mitotic cell cycle / substrate adhesion-dependent cell spreading / post-embryonic development / protein kinase C binding / positive regulation of release of sequestered calcium ion into cytosol / positive regulation of endothelial cell migration / thymus development / regulation of autophagy / neural tube closure / integrin-mediated signaling pathway / establishment of localization in cell / regulation of actin cytoskeleton organization Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.15 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 | 6npe.cif.gz | 129.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6npe.ent.gz | 98.4 KB | Display | PDB format |
PDBx/mmJSON format | 6npe.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/np/6npe ftp://data.pdbj.org/pub/pdb/validation_reports/np/6npe | 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 frugiperda (fall armyworm) References: UniProt: P00519, non-specific protein-tyrosine kinase |
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-Non-polymers , 5 types, 188 molecules
#2: Chemical | ChemComp-SO4 / #3: Chemical | #4: Chemical | #5: Chemical | ChemComp-2PE / | #6: 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: 2.96 Å3/Da / Density % sol: 58.42 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion Details: 20 mM Tris-HCl [pH 8.0] 100 mM NaCl 3 mM DTT, and 5% (v/v) glycerol. 1-3 % PEG300, 2M AmSO4 Cryo: 20% glycerol |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9764 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: May 22, 2008 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9764 Å / Relative weight: 1 |
Reflection | Resolution: 2.15→49.4 Å / Num. obs: 43967 / % possible obs: 95 % / Redundancy: 5.5 % / Net I/σ(I): 16.9 |
Reflection shell | Resolution: 2.15→2.23 Å |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.15→49.4 Å / SU ML: 0.21 / Cross valid method: THROUGHOUT / σ(F): 1.35 / Phase error: 21.75
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 113.84 Å2 / Biso mean: 38.9698 Å2 / Biso min: 18.47 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.15→49.4 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 19
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