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- PDB-4cli: Structure of the Human Anaplastic Lymphoma Kinase in Complex with... -
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Open data
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Basic information
Entry | Database: PDB / ID: 4cli | ||||||
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Title | Structure of the Human Anaplastic Lymphoma Kinase in Complex with PF- 06463922 ((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). | ||||||
![]() | ALK TYROSINE KINASE RECEPTOR | ||||||
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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 / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | McTigue, M.A. / Deng, Y.L. / Liu, W. / Brooun, A. / Stewart, A.E. | ||||||
![]() | ![]() 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 Alk/Ros1 with Pre-Clinical 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.M. / Engstrom, L.D. / He, M. / Hoffman, J.E. / ...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.M. / Engstrom, L.D. / He, M. / Hoffman, J.E. / Hoffman, R.L. / Huang, Q. / Kath, J. / Kania, R.S. / Lam, H. / Lam, J.L. / Le, P.T. / Lingardo, L. / Liu, W. / Mctigue, M.A. / Palmer, C.L. / Sach, N.W. / Smeal, T. / Smith, G.L. / Stewart, A.E. / Timofeevski, S.L. / 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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Download
PDBx/mmCIF format | ![]() | 80.2 KB | Display | ![]() |
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PDB format | ![]() | 58.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 4cljC ![]() 4cmoC ![]() 4cmtC ![]() 4cmuC ![]() 4cnhC ![]() 4ctbC ![]() 4ctcC ![]() 5kz0C ![]() 2xp2S C: citing same article ( S: Starting model for refinement |
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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: TYROSINE KINASE DOMAIN, RESIDUES 1093-1411 Source method: isolated from a genetically manipulated source Details: NONPHOSPHORYLATED / Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() References: UniProt: Q9UM73, ![]() |
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#2: Chemical | ChemComp-5P8 / (![]() |
#3: Water | ChemComp-HOH / ![]() |
Sequence details | RESIDUES 1093-1411 OF HUMAN ANAPLASTIC |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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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: 5.5 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 PILATUS 6M / Detector: PIXEL / Date: Feb 3, 2012 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength![]() |
Reflection | Resolution: 1.94→52.51 Å / Num. obs: 23831 / % possible obs: 99.9 % / Observed criterion σ(I): 1 / Redundancy: 6.5 % / Biso Wilson estimate: 16 Å2 / Rmerge(I) obs: 0.11 / Net I/σ(I): 12.6 |
Reflection shell | Resolution: 1.94→1.99 Å / Redundancy: 6.4 % / Rmerge(I) obs: 0.77 / Mean I/σ(I) obs: 2.8 / % possible all: 99.8 |
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Processing
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Refinement | Method to determine structure![]() ![]() Starting model: PDB ENTRY 2XP2 Resolution: 2.05→52.51 Å / Rfactor Rfree error: 0.007 / Data cutoff high absF: 31364.93 / 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: 62.8196 Å2 / ksol: 0.380114 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 29.2 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.05→52.51 Å
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Refine LS restraints |
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Refine LS restraints NCS | NCS model details: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 2.05→2.18 Å / Rfactor Rfree error: 0.026 / Total num. of bins used: 6
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Xplor file |
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