+Open data
-Basic information
Entry | Database: PDB / ID: 2yhv | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of L1196M Mutant Anaplastic Lymphoma Kinase | ||||||
Components | ALK TYROSINE KINASE RECEPTOR | ||||||
Keywords | TRANSFERASE / RECEPTOR | ||||||
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: 1.9 Å | ||||||
Authors | McTigue, M. / Deng, Y. / Liu, W. / Brooun, A. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2014 Title: Design of Potent and Selective Inhibitors to Overcome Clinical Anaplastic Lymphoma Kinase 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.S. / Cui, J.J. / Dack, K.N. / Deal, J.G. / Deng, Y. / Dinh, D. / Engstrom, L.D. / ...Authors: Huang, Q. / Johnson, T.W. / Bailey, S. / Brooun, A. / Bunker, K.D. / Burke, B.J. / Collins, M.R. / Cook, A.S. / Cui, J.J. / Dack, K.N. / Deal, J.G. / Deng, Y. / Dinh, D. / Engstrom, L.D. / He, M. / Hoffman, J. / Hoffman, R.L. / Johnson, P.S. / Kania, R.S. / Lam, H. / Lam, J.L. / Le, P.T. / Li, Q. / Lingardo, L. / Liu, W. / Lu, M.W. / Mctigue, M. / Palmer, C.L. / Richardson, P.F. / Sach, N.W. / Shen, H. / Smeal, T. / Smith, G.L. / Stewart, A.E. / Timofeevski, S. / Tsaparikos, K. / Wang, H. / Zhu, H. / Zhu, J. / Zou, H.Y. / Edwards, M.P. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 2yhv.cif.gz | 77 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb2yhv.ent.gz | 55.5 KB | Display | PDB format |
PDBx/mmJSON format | 2yhv.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yh/2yhv ftp://data.pdbj.org/pub/pdb/validation_reports/yh/2yhv | HTTPS FTP |
---|
-Related structure data
Related structure data | 2yfxSC 4anlC 4anqC 4ccbC 4ccuC 4cd0C S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 38614.160 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN, RESIDUES 1093-1411 / Mutation: YES Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Cell line (production host): SF9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) References: UniProt: Q9UM73, receptor protein-tyrosine kinase |
---|---|
#2: Water | ChemComp-HOH / |
Compound details | ENGINEERED |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.27 Å3/Da / Density % sol: 45.33 % / Description: NONE |
---|---|
Crystal grow | Temperature: 286 K / Method: vapor diffusion / pH: 8.4 Details: CRYSTALS WERE GROWN AT 13 DEGREE CELSIUS BY VAPOR DIFFUSION AFTER MIXING 2 MICROLITERS OF PROTEIN SOLUTION WITH 2 MICROLITERS OF A RESERVOIR SOLUITON CONTAINING: 0.1 M TRIS PH 8.4, 0.2 M ...Details: CRYSTALS WERE GROWN AT 13 DEGREE CELSIUS BY VAPOR DIFFUSION AFTER MIXING 2 MICROLITERS OF PROTEIN SOLUTION WITH 2 MICROLITERS OF A RESERVOIR SOLUITON CONTAINING: 0.1 M TRIS PH 8.4, 0.2 M LITHIUM SULFATE, 0.1% (W/V) B-OCTYLGLUCOSIDE, AND 20% (W/V) PEG 3350. |
-Data collection
Diffraction | Mean temperature: 93 K |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 |
Detector | Type: ADSC QUANTUM 210 / Detector: CCD / Date: Nov 4, 2010 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.89→105.19 Å / Num. obs: 25946 / % possible obs: 99.8 % / Observed criterion σ(I): 1 / Redundancy: 6.4 % / Biso Wilson estimate: 22.2 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 18.7 |
Reflection shell | Resolution: 1.89→2 Å / Redundancy: 6.7 % / Rmerge(I) obs: 0.47 / Mean I/σ(I) obs: 3.9 / % possible all: 99.9 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 2YFX Resolution: 1.9→52.6 Å / Rfactor Rfree error: 0.009 / Data cutoff high absF: 1211445.63 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Solvent model: FLAT MODEL / Bsol: 48.0599 Å2 / ksol: 0.370058 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 31.2 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.9→52.6 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints NCS | NCS model details: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.9→2.02 Å / Rfactor Rfree error: 0.028 / Total num. of bins used: 6
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Xplor file |
|