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Yorodumi- PDB-5ftq: Crystal structure of the ALK kinase domain in complex with Cmpd 17 -
+Open data
-Basic information
Entry | Database: PDB / ID: 5ftq | ||||||
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Title | Crystal structure of the ALK kinase domain in complex with Cmpd 17 | ||||||
Components | ALK TYROSINE KINASE RECEPTOR | ||||||
Keywords | TRANSFERASE / KINASE INHIBITORS / CANCER / DRUG DISCOVERY / ALK / TRK / ROS1 / ANAPLASTIC LARGE CELL LYMPHOMA (ALCL) / NON SMALL CELL LARGE CANCER (NSCLC) / NEUROBLASTOMA / COLORECTAL CANCER (CRC) | ||||||
Function / homology | Function and homology information response to environmental enrichment / ASP-3026-resistant ALK mutants / NVP-TAE684-resistant ALK mutants / alectinib-resistant ALK mutants / brigatinib-resistant ALK mutants / ceritinib-resistant ALK mutants / crizotinib-resistant ALK mutants / lorlatinib-resistant ALK mutants / receptor signaling protein tyrosine kinase activator activity / regulation of dopamine receptor signaling pathway ...response to environmental enrichment / ASP-3026-resistant ALK mutants / NVP-TAE684-resistant ALK mutants / alectinib-resistant ALK mutants / brigatinib-resistant ALK mutants / ceritinib-resistant ALK mutants / crizotinib-resistant ALK mutants / lorlatinib-resistant ALK mutants / receptor signaling protein tyrosine kinase activator activity / regulation of dopamine receptor signaling pathway / ALK mutants bind TKIs / swimming behavior / positive regulation of dendrite development / regulation of neuron differentiation / adult behavior / Signaling by ALK / Signaling by ALK fusions and activated point mutants / neuron development / Nuclear events stimulated by ALK signaling in cancer / negative regulation of lipid catabolic process / energy homeostasis / peptidyl-tyrosine autophosphorylation / transmembrane receptor protein tyrosine kinase activity / hippocampus development / receptor protein-tyrosine kinase / cell surface receptor protein tyrosine kinase signaling pathway / heparin binding / positive regulation of NF-kappaB transcription factor activity / regulation of cell population proliferation / protein tyrosine kinase activity / regulation of apoptotic process / protein autophosphorylation / receptor complex / phosphorylation / signal transduction / protein-containing complex / extracellular exosome / ATP binding / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | HOMO SAPIENS (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.7 Å | ||||||
Authors | Bossi, R. / Canevari, G. / Fasolini, M. / Menichincheri, M. / Ardini, E. / Magnaghi, P. / Avanzi, N. / Banfi, P. / Buffa, L. / Ceriani, L. ...Bossi, R. / Canevari, G. / Fasolini, M. / Menichincheri, M. / Ardini, E. / Magnaghi, P. / Avanzi, N. / Banfi, P. / Buffa, L. / Ceriani, L. / Colombo, M. / Corti, L. / Donati, D. / Felder, E. / Fiorelli, C. / Fiorentini, F. / Galvani, A. / Isacchi, A. / Lombardi Borgia, A. / Marchionni, C. / Nesi, M. / Orrenius, C. / Panzeri, A. / Perrone, E. / Pesenti, E. / Rusconi, L. / Saccardo, M.B. / Vanotti, E. / Orsini, P. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2016 Title: Discovery of Entrectinib: A New 3-Aminoindazole as a Potent Anaplastic Lymphoma Kinase (Alk), C-Ros Oncogene 1 Kinase (Ros1), and Pan-Tropomyosin Receptor Kinases (Pan-Trks) Inhibitor. Authors: Menichincheri, M. / Ardini, E. / Magnaghi, P. / Avanzi, N. / Banfi, P. / Bossi, R.T. / Buffa, L. / Canevari, G. / Ceriani, L. / Colombo, M. / Corti, L. / Donati, D. / Fasolini, M. / Felder, ...Authors: Menichincheri, M. / Ardini, E. / Magnaghi, P. / Avanzi, N. / Banfi, P. / Bossi, R.T. / Buffa, L. / Canevari, G. / Ceriani, L. / Colombo, M. / Corti, L. / Donati, D. / Fasolini, M. / Felder, E.R. / Fiorelli, C. / Fiorentini, F. / Galvani, A. / Isacchi, A. / Borgia, A.L. / Marchionni, C. / Nesi, M. / Orrenius, C. / Panzeri, A. / Pesenti, E. / Rusconi, L. / Saccardo, B.M. / Vanotti, E. / Perrone, E. / Orsini, P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5ftq.cif.gz | 82.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5ftq.ent.gz | 60.6 KB | Display | PDB format |
PDBx/mmJSON format | 5ftq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ft/5ftq ftp://data.pdbj.org/pub/pdb/validation_reports/ft/5ftq | HTTPS FTP |
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-Related structure data
Related structure data | 5ftoC 2xbaS 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: 35334.617 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN, UNP RESIDUES 1094-1407 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PVL-GST-ALK-KD / Cell line (production host): SF9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) References: UniProt: Q9UM73, receptor protein-tyrosine kinase |
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#2: Chemical | ChemComp-U4W / |
#3: Chemical | ChemComp-GOL / |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.28 Å3/Da / Density % sol: 46 % / Description: NONE |
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Crystal grow | Details: 18% PEG3350, 0.1 M TRIS/HCL PH 8.5 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 1.0723 |
Detector | Type: ADSC CCD / Detector: CCD / Date: Dec 6, 2007 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.0723 Å / Relative weight: 1 |
Reflection | Resolution: 1.7→58.32 Å / Num. obs: 34703 / % possible obs: 97 % / Observed criterion σ(I): 2 / Redundancy: 4.2 % / Rmerge(I) obs: 0.05 / Net I/σ(I): 19.6 |
Reflection shell | Resolution: 1.7→1.79 Å / Redundancy: 4.3 % / Rmerge(I) obs: 0.28 / Mean I/σ(I) obs: 4.1 / % possible all: 96.5 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 2XBA Resolution: 1.7→50.96 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.942 / Cross valid method: THROUGHOUT / ESU R: 0.107 / ESU R Free: 0.111 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
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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 mean: 25.786 Å2
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Refinement step | Cycle: LAST / Resolution: 1.7→50.96 Å
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