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Yorodumi- PDB-5fto: Crystal structure of the ALK kinase domain in complex with Entrectinib -
+Open data
-Basic information
Entry | Database: PDB / ID: 5fto | ||||||
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Title | Crystal structure of the ALK kinase domain in complex with Entrectinib | ||||||
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 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 / MDK and PTN in ALK signaling / receptor signaling protein tyrosine kinase activator activity / regulation of dopamine receptor signaling pathway ...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 / MDK and PTN in ALK signaling / receptor signaling protein tyrosine kinase activator activity / regulation of dopamine receptor signaling pathway / response to environmental enrichment / ALK mutants bind TKIs / swimming behavior / positive regulation of dendrite development / regulation of neuron differentiation / Signaling by ALK / adult behavior / peptidyl-tyrosine autophosphorylation / neuron development / transmembrane receptor protein tyrosine kinase activity / negative regulation of lipid catabolic process / energy homeostasis / cell surface receptor protein tyrosine kinase signaling pathway / phosphorylation / hippocampus development / receptor protein-tyrosine kinase / Signaling by ALK fusions and activated point mutants / positive regulation of NF-kappaB transcription factor activity / heparin binding / regulation of cell population proliferation / protein tyrosine kinase activity / regulation of apoptotic process / protein autophosphorylation / receptor complex / 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 / MOLECULAR REPLACEMENT / Resolution: 2.22 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 | 5fto.cif.gz | 76.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5fto.ent.gz | 56 KB | Display | PDB format |
PDBx/mmJSON format | 5fto.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5fto_validation.pdf.gz | 729.4 KB | Display | wwPDB validaton report |
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Full document | 5fto_full_validation.pdf.gz | 734.8 KB | Display | |
Data in XML | 5fto_validation.xml.gz | 15.9 KB | Display | |
Data in CIF | 5fto_validation.cif.gz | 22.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ft/5fto ftp://data.pdbj.org/pub/pdb/validation_reports/ft/5fto | HTTPS FTP |
-Related structure data
Related structure data | 5ftqC 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-YMX / |
#3: 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: 2.3 Å3/Da / Density % sol: 47 % / Description: NONE |
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Crystal grow | pH: 8.5 / 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: ROTATING ANODE / Type: RIGAKU / Wavelength: 1.5417 |
Detector | Type: MAR scanner 345 mm plate / Detector: IMAGE PLATE / Date: Apr 10, 2007 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5417 Å / Relative weight: 1 |
Reflection | Resolution: 2.21→35.03 Å / Num. obs: 16537 / % possible obs: 97.5 % / Observed criterion σ(I): 2 / Redundancy: 5.8 % / Rmerge(I) obs: 0.12 / Net I/σ(I): 13.5 |
Reflection shell | Resolution: 2.21→2.32 Å / Redundancy: 5.5 % / Rmerge(I) obs: 0.53 / Mean I/σ(I) obs: 3.2 / % possible all: 83.4 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 2XBA Resolution: 2.22→31.34 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.898 / Cross valid method: THROUGHOUT / ESU R: 0.308 / ESU R Free: 0.236 / 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: 25.973 Å2
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Refinement step | Cycle: LAST / Resolution: 2.22→31.34 Å
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Refine LS restraints |
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