[English] 日本語
Yorodumi- PDB-5aac: Structure of C1156Y Mutant Human Anaplastic Lymphoma Kinase in Co... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5aac | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of C1156Y Mutant Human Anaplastic Lymphoma Kinase in Complex with Crizotinib | ||||||
Components | ALK TYROSINE KINASE RECEPTOR | ||||||
Keywords | TRANSFERASE / RECEPTOR TYROSINE KINASE / ANAPLASTIC LYMPHOMA KINASE / INHIBITOR / MUTANT | ||||||
Function / homology | Function and homology information 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 / peptidyl-tyrosine autophosphorylation / neuron development / transmembrane receptor protein tyrosine kinase activity / negative regulation of lipid catabolic process / energy homeostasis / cell surface receptor protein tyrosine kinase signaling pathway / 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 | HOMO SAPIENS (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.7 Å | ||||||
Authors | McTigue, M. / Deng, Y. / Liu, W. / Brooun, A. / Stewart, A. | ||||||
Citation | Journal: N.Engl.J.Med. / Year: 2016 Title: Resensitization to Crizotinib by the Lorlatinib Alk Resistance Mutation L1198F. Authors: Shaw, A.T. / Friboulet, L. / Leshchiner, I. / Gainor, J.F. / Bergqvist, S. / Brooun, A. / Burke, B.J. / Deng, Y. / Liu, W. / Dardaei, L. / Frias, R.L. / Schultz, K.R. / Logan, J. / James, L. ...Authors: Shaw, A.T. / Friboulet, L. / Leshchiner, I. / Gainor, J.F. / Bergqvist, S. / Brooun, A. / Burke, B.J. / Deng, Y. / Liu, W. / Dardaei, L. / Frias, R.L. / Schultz, K.R. / Logan, J. / James, L.P. / Smeal, T. / Timofeevski, S. / Katayama, R. / Iafrate, A.J. / Le, L. / Mctigue, M. / Getz, G. / Johnson, T.W. / Engelman, J.A. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 5aac.cif.gz | 78.5 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb5aac.ent.gz | 58 KB | Display | PDB format |
PDBx/mmJSON format | 5aac.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5aac_validation.pdf.gz | 687.1 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 5aac_full_validation.pdf.gz | 692.9 KB | Display | |
Data in XML | 5aac_validation.xml.gz | 9.2 KB | Display | |
Data in CIF | 5aac_validation.cif.gz | 13.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/aa/5aac ftp://data.pdbj.org/pub/pdb/validation_reports/aa/5aac | HTTPS FTP |
-Related structure data
Related structure data | 5a9uC 5aa8C 5aa9C 5aaaC 5aabC 2xp2S C: citing same article (ref.) S: Starting model for refinement |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 36969.387 Da / Num. of mol.: 1 / Fragment: TYROSINE KINASE DOMAIN, UNP 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 |
---|---|
#2: Chemical | ChemComp-VGH / |
#3: Water | ChemComp-HOH / |
Sequence details | RESIDUES 1093-1411, CONTAINING MUTATION C1156Y, OF HUMAN ANAPLASTIC LYMPHOMA KINASE PLUS AN ...RESIDUES 1093-1411, CONTAINING |
-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 % / Description: NONE |
---|---|
Crystal grow | Temperature: 286 K / Method: vapor diffusion, hanging drop / pH: 8 Details: HANGING DROP VAPOR DIFFUSION AT 13 DEGREES C. 2 MICROLITERS OF PURIFIED PROTEIN SOLUTION (11-15 MG/ML) CONTAINING INHIBITOR COMPOUND AT A 2X STOICHIOMETRY OF INHIBITOR TO PROTEIN WERE ...Details: HANGING DROP VAPOR DIFFUSION AT 13 DEGREES C. 2 MICROLITERS OF PURIFIED PROTEIN SOLUTION (11-15 MG/ML) CONTAINING INHIBITOR COMPOUND AT A 2X STOICHIOMETRY OF INHIBITOR TO PROTEIN WERE COMBINED WITH 2 MICROLITERS OF SOLUTIONS CONTAINING: 0.2 M LITHIUM SULFATE, 17-21% PEG3350 AND 0.1M TRIS PH 7.6-8.5. |
-Data collection
Diffraction | Mean temperature: 87 K |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.9795 |
Detector | Type: MARRESEARCH RAYONIX 300 / Detector: CCD / Date: May 15, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 1.63→50 Å / Num. obs: 39562 / % possible obs: 99.9 % / Observed criterion σ(I): 1 / Redundancy: 6 % / Biso Wilson estimate: 22.8 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 24.9 |
Reflection shell | Resolution: 1.63→1.69 Å / Redundancy: 6.1 % / Rmerge(I) obs: 0.89 / Mean I/σ(I) obs: 3 / % possible all: 100 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 2XP2 Resolution: 1.7→38.66 Å / Rfactor Rfree error: 0.007 / Data cutoff high absF: 1237953.97 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Solvent model: FLAT MODEL / Bsol: 55.463 Å2 / ksol: 0.379633 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 32.6 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.7→38.66 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints NCS | NCS model details: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.7→1.81 Å / Rfactor Rfree error: 0.021 / Total num. of bins used: 6
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Xplor file |
|