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- PDB-5kz0: Structure of Human Anaplastic Lymphoma Kinase in Complex With 2-[... -
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Open data
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Basic information
Entry | Database: PDB / ID: 5kz0 | ||||||
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Title | Structure of Human Anaplastic Lymphoma Kinase in Complex With 2-[(1R)-1-{[2-amino-5-(1,3-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl]oxy}ethyl]-4-fluoro-N,N-dimethylbenzamide | ||||||
![]() | ALK tyrosine kinase receptor | ||||||
![]() | Transferase/Transferase Inhibitor / kinase / inhibitor / Transferase-Transferase Inhibitor complex | ||||||
Function / homology | ![]() 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 / neuron development / negative regulation of lipid catabolic process / peptidyl-tyrosine autophosphorylation / energy homeostasis / cell surface receptor protein tyrosine kinase signaling pathway / transmembrane receptor protein tyrosine kinase activity / 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 | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | McTigue, M. / Deng, Y.L. / Liu, W. / Brooun, A. | ||||||
![]() | ![]() Title: Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a ...Title: Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. Authors: Johnson, T.W. / Richardson, P.F. / Bailey, S. / Brooun, A. / Burke, B.J. / Collins, M.R. / Cui, J.J. / Deal, J.G. / Deng, Y.L. / Dinh, D. / Engstrom, L.D. / He, M. / Hoffman, J. / Hoffman, R. ...Authors: Johnson, T.W. / Richardson, P.F. / Bailey, S. / Brooun, A. / Burke, B.J. / Collins, M.R. / Cui, J.J. / Deal, J.G. / Deng, Y.L. / Dinh, D. / Engstrom, L.D. / He, M. / Hoffman, J. / Hoffman, R.L. / Huang, Q. / Kania, R.S. / Kath, J.C. / Lam, H. / Lam, J.L. / Le, P.T. / Lingardo, L. / Liu, W. / McTigue, M. / Palmer, C.L. / Sach, N.W. / Smeal, T. / Smith, G.L. / Stewart, A.E. / Timofeevski, S. / Zhu, H. / Zhu, J. / Zou, H.Y. / Edwards, M.P. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 78.8 KB | Display | ![]() |
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PDB format | ![]() | 56.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 4cliSC ![]() 4cljC ![]() 4cmoC ![]() 4cmtC ![]() 4cmuC ![]() 4cnhC ![]() 4ctbC ![]() 4ctcC S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 36909.355 Da / Num. of mol.: 1 / Fragment: UNP residues 1093-1411 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q9UM73, receptor protein-tyrosine kinase |
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#2: Chemical | ChemComp-6YL / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.09 Å3/Da / Density % sol: 41.19 % |
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Crystal grow | Temperature: 286 K / Method: vapor diffusion, hanging drop Details: HANGING DROP VAPOR DIFFUSION AT 13 DEGREES C. EQUAL VOLUMES OF PURIFIED PROTEIN SOLUTION(APPROXIMATELY 13-15 MG/ML)CONTAINING 0.0011M INHIBITOR COMPOUND WERE COMBINED WITH A SOLUTION ...Details: HANGING DROP VAPOR DIFFUSION AT 13 DEGREES C. EQUAL VOLUMES OF PURIFIED PROTEIN SOLUTION(APPROXIMATELY 13-15 MG/ML)CONTAINING 0.0011M INHIBITOR COMPOUND WERE COMBINED WITH A SOLUTION CONTAINING: 0.15M AMMONIUM SULFATE, 9-10.5% MONOMETHYLETHER PEG5K AND 0.1M MES IN THE PH RANGE 5.3-6.5 |
-Data collection
Diffraction | Mean temperature: 87 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Feb 3, 2012 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.976 Å / Relative weight: 1 |
Reflection | Resolution: 2.16→500 Å / Num. obs: 20573 / % possible obs: 99.9 % / Redundancy: 6.5 % / Net I/σ(I): 7 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 4cli Resolution: 2.3→51.74 Å / Cross valid method: FREE R-VALUE / σ(F): 1776
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Displacement parameters | Biso max: 73.05 Å2 / Biso mean: 25.4667 Å2 / Biso min: 2.1 Å2
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Refinement step | Cycle: final / Resolution: 2.3→51.74 Å
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Refine LS restraints |
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Xplor file |
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