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Yorodumi- PDB-4cd0: Structure of L1196M Mutant Human Anaplastic Lymphoma Kinase in Co... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4cd0 | ||||||
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Title | Structure of L1196M Mutant Human Anaplastic Lymphoma Kinase in Complex with 2-(5-(6-amino-5-((R)-1-(5-fluoro-2-(2H-1,2,3-triazol-2- yl)phenyl)ethoxy)pyridin-3-yl)-4-methylthiazol-2-yl)propane-1,2-diol | ||||||
Components | ALK TYROSINE KINASE RECEPTOR | ||||||
Keywords | TRANSFERASE / RECEPTOR TYROSINE KINASE / INHIBITOR | ||||||
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: 2.23 Å | ||||||
Authors | McTigue, M. / Deng, Y. / Liu, W. / Brooun, A. / Stewart, A. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2014 Title: The Design of Potent and Selective Inhibitors to Overcome Clinical Alk Mutations Resistant to Crizotinib. Authors: Huang, Q. / Johnson, T.W. / Bailey, S. / Brooun, A. / Bunker, K.D. / Burke, B.J. / Collins, M.R. / Cook, A. / Cui, J.J. / Dack, K.N. / Deal, J.G. / Deng, Y. / Dinh, D.M. / Engstrom, L.D. / ...Authors: Huang, Q. / Johnson, T.W. / Bailey, S. / Brooun, A. / Bunker, K.D. / Burke, B.J. / Collins, M.R. / Cook, A. / Cui, J.J. / Dack, K.N. / Deal, J.G. / Deng, Y. / Dinh, D.M. / Engstrom, L.D. / He, M. / Hoffman, J. / Hoffman, R.L. / Shen, H. / Johnson, P. / Kania, R.S. / Lam, H. / Lam, J.L. / Le, P. / Li, Q. / Lingardo, L. / Liu, W. / West Lu, M. / Mctigue, M.A. / Palmer, C.L. / Richardson, P.F. / Sach, N.W. / Smeal, T. / Smith, G.L. / Stewart, A.E. / Timofeevski, S.L. / Tsaparikos, K. / Wang, H. / Zhu, H. / Zhu, J. / Zou, H.Y. / Edwards, M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4cd0.cif.gz | 79.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4cd0.ent.gz | 57.1 KB | Display | PDB format |
PDBx/mmJSON format | 4cd0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cd/4cd0 ftp://data.pdbj.org/pub/pdb/validation_reports/cd/4cd0 | HTTPS FTP |
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-Related structure data
Related structure data | 2yfxC 2yhvC 4anlC 4anqC 4ccbC 4ccuC 2xp2S 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: 38614.160 Da / Num. of mol.: 1 / Fragment: TYROSINE KINASE DOMAIN, RESIDUES 1093-1411 / Mutation: YES Source method: isolated from a genetically manipulated source Details: NONPHOSPHORYLATED / Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PFASTBAC / 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-AWJ / ( |
#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: 2.1 Å3/Da / Density % sol: 41 % / Description: NONE |
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Crystal grow | Temperature: 286 K / Method: vapor diffusion, hanging drop / pH: 8.5 Details: HANGING DROP VAPOR DIFFUSION AT 13 DEGREES C. EQUAL VOLUMES OF PURIFIED PROTEIN SOLUTION (APPROXIMATELY 11.3 MG/ML)CONTAINING 0.001 M INHIBITOR COMPOUND WERE COMBINED WITH A SOLUTION ...Details: HANGING DROP VAPOR DIFFUSION AT 13 DEGREES C. EQUAL VOLUMES OF PURIFIED PROTEIN SOLUTION (APPROXIMATELY 11.3 MG/ML)CONTAINING 0.001 M INHIBITOR COMPOUND WERE COMBINED WITH A SOLUTION CONTAINING: 0.2 M LITHIUM SULFATE, 18% PEG5K AND 0.1M TRIS PH 8.5. |
-Data collection
Diffraction | Mean temperature: 83 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 20, 2012 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.23→57.27 Å / Num. obs: 15697 / % possible obs: 99.9 % / Observed criterion σ(I): 1 / Redundancy: 6.4 % / Biso Wilson estimate: 35.3 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 21.8 |
Reflection shell | Resolution: 2.23→2.36 Å / Redundancy: 6.6 % / Rmerge(I) obs: 0.46 / Mean I/σ(I) obs: 3.8 / % possible all: 99.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 2XP2 Resolution: 2.23→52.33 Å / Rfactor Rfree error: 0.012 / Data cutoff high absF: 1060447.94 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 47.3131 Å2 / ksol: 0.372227 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 37.8 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.23→52.33 Å
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Refine LS restraints |
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Refine LS restraints NCS | NCS model details: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 2.23→2.37 Å / Rfactor Rfree error: 0.035 / Total num. of bins used: 6
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Xplor file |
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