[English] 日本語
Yorodumi- PDB-4ccb: Structure of the Human Anaplastic Lymphoma Kinase in Complex with... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4ccb | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of the Human Anaplastic Lymphoma Kinase in Complex with 3-((R)-1-(5-fluoro-2-(2H-1,2,3-triazol-2-yl)phenyl)ethoxy)-5-(5-methyl-1H- pyrazol-4-yl)pyridin-2-amine | ||||||
Components | ALK TYROSINE KINASE RECEPTOR | ||||||
Keywords | TRANSFERASE / RECEPTOR TYROSINE KINASE / ANAPLASTIC LYMPHOMA 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: 2.03 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 |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 4ccb.cif.gz | 77.1 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb4ccb.ent.gz | 55.7 KB | Display | PDB format |
PDBx/mmJSON format | 4ccb.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cc/4ccb ftp://data.pdbj.org/pub/pdb/validation_reports/cc/4ccb | HTTPS FTP |
---|
-Related structure data
Related structure data | 2yfxC 2yhvC 4anlC 4anqC 4ccuC 4cd0C 2xp2S S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-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.) HOMO SAPIENS (human) / Plasmid: PFASTBAC / Cell line (production host): SF9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) References: UniProt: Q9UM73, receptor protein-tyrosine kinase |
---|---|
#2: Chemical | ChemComp-OFG / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.1 Å3/Da / Density % sol: 41.4 % / Description: NONE |
---|---|
Crystal grow | Temperature: 286 K / Method: vapor diffusion, hanging drop / pH: 5.6 Details: CRYSTALLIZATION CONDITIONS: HANGING DROP VAPOR DIFFUSION AT 13 DEGREES C. EQUAL VOLUMES OF PURIFIED PROTEIN SOLUTION (APPROXIMATELY 13-15 MG/ML)CONTAINING 0.001 M INHIBITOR COMPOUND WERE ...Details: CRYSTALLIZATION CONDITIONS: HANGING DROP VAPOR DIFFUSION AT 13 DEGREES C. EQUAL VOLUMES OF PURIFIED PROTEIN SOLUTION (APPROXIMATELY 13-15 MG/ML)CONTAINING 0.001 M INHIBITOR COMPOUND WERE COMBINED WITH A SOLUTION CONTAINING: 0.15 M 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 |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Type: ALS / Wavelength: 0.977 |
Detector | Type: ADSC CCD / Detector: CCD / Date: Jan 29, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.977 Å / Relative weight: 1 |
Reflection | Resolution: 1.88→50 Å / Num. obs: 26123 / % possible obs: 99.7 % / Observed criterion σ(I): 1 / Redundancy: 6.8 % / Biso Wilson estimate: 16.4 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 3.4 |
Reflection shell | Resolution: 1.88→1.91 Å / Redundancy: 5.2 % / Rmerge(I) obs: 0.6 / Mean I/σ(I) obs: 3.1 / % possible all: 95.6 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 2XP2 Resolution: 2.03→46.27 Å / Rfactor Rfree error: 0.01 / Data cutoff high absF: 69529.02 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Solvent model: FLAT MODEL / Bsol: 49.7444 Å2 / ksol: 0.374721 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 30 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.03→46.27 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints NCS | NCS model details: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 2.03→2.16 Å / Rfactor Rfree error: 0.027 / Total num. of bins used: 6
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Xplor file |
|