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Yorodumi- PDB-5aa8: Structure of C1156Y,L1198F Mutant Human Anaplastic Lymphoma Kinas... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5aa8 | ||||||
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Title | Structure of C1156Y,L1198F Mutant 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). | ||||||
Components | ALK TYROSINE KINASE RECEPTOR | ||||||
Keywords | TRANSFERASE / RECEPTOR TYROSINE 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: 1.86 Å | ||||||
Authors | McTigue, M. / Deng, Y.-L. / 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 |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5aa8.cif.gz | 76.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5aa8.ent.gz | 56.5 KB | Display | PDB format |
PDBx/mmJSON format | 5aa8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5aa8_validation.pdf.gz | 827.7 KB | Display | wwPDB validaton report |
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Full document | 5aa8_full_validation.pdf.gz | 835.3 KB | Display | |
Data in XML | 5aa8_validation.xml.gz | 15.5 KB | Display | |
Data in CIF | 5aa8_validation.cif.gz | 21.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/aa/5aa8 ftp://data.pdbj.org/pub/pdb/validation_reports/aa/5aa8 | HTTPS FTP |
-Related structure data
Related structure data | 5a9uC 5aa9C 5aaaC 5aabC 5aacC 4cljS C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 37003.402 Da / Num. of mol.: 1 / Fragment: TYROSINE KINASE DOMAIN, 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 |
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#2: Chemical | ChemComp-5P8 / ( |
#3: Water | ChemComp-HOH / |
Sequence details | RESIDUES 1093-1411, CONTAINING MUTATIONS C1156Y AND L1198F, OF HUMAN ANAPLASTIC LYMPHOMA KINASE ...RESIDUES 1093-1411, CONTAINING |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.1 Å3/Da / Density % sol: 41.35 % / Description: NONE |
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Crystal grow | pH: 8 / Details: pH 8 |
-Data collection
Diffraction | Mean temperature: 87 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 0.9795 |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 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: 1.86→104.93 Å / Num. obs: 26219 / % possible obs: 97.4 % / Observed criterion σ(I): 1 / Redundancy: 6 % / Biso Wilson estimate: 26.2 Å2 / Rmerge(I) obs: 0.08 / Net I/σ(I): 14.5 |
Reflection shell | Resolution: 1.86→2.01 Å / Redundancy: 4.3 % / Rmerge(I) obs: 0.51 / Mean I/σ(I) obs: 2.6 / % possible all: 87.6 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 4CLJ Resolution: 1.86→52.46 Å / Rfactor Rfree error: 0.008 / Data cutoff high absF: 1201702.7 / 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: 46.54 Å2 / ksol: 0.374951 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 33.9 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 1.86→52.46 Å
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Refine LS restraints |
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Refine LS restraints NCS | NCS model details: NONE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.86→1.98 Å / Rfactor Rfree error: 0.029 / Total num. of bins used: 6
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