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Yorodumi- PDB-5tc0: Structure-based optimization of 1H-imidazole-2-carboxamides as Ax... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5tc0 | ||||||
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Title | Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate | ||||||
Components | Tyrosine-protein kinase Mer | ||||||
Keywords | Transferase/Transferase Inhibitor / kinase / inhibitor / surrogate / oncology / Transferase-Transferase Inhibitor complex | ||||||
Function / homology | Function and homology information negative regulation of leukocyte apoptotic process / negative regulation of lymphocyte activation / neutrophil clearance / natural killer cell differentiation / secretion by cell / negative regulation of cytokine production / vagina development / photoreceptor outer segment / positive regulation of phagocytosis / phagocytosis ...negative regulation of leukocyte apoptotic process / negative regulation of lymphocyte activation / neutrophil clearance / natural killer cell differentiation / secretion by cell / negative regulation of cytokine production / vagina development / photoreceptor outer segment / positive regulation of phagocytosis / phagocytosis / transmembrane receptor protein tyrosine kinase activity / substrate adhesion-dependent cell spreading / phosphatidylinositol 3-kinase/protein kinase B signal transduction / establishment of localization in cell / Cell surface interactions at the vascular wall / receptor protein-tyrosine kinase / platelet activation / cell surface receptor protein tyrosine kinase signaling pathway / cell migration / retina development in camera-type eye / cell-cell signaling / nervous system development / spermatogenesis / cell surface receptor signaling pathway / receptor complex / protein phosphorylation / extracellular space / ATP binding / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.24 Å | ||||||
Authors | Hoffman, I.D. / Lawson, J.D. | ||||||
Citation | Journal: Bioorg. Med. Chem. Lett. / Year: 2017 Title: Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate. Authors: Keung, W. / Boloor, A. / Brown, J. / Kiryanov, A. / Gangloff, A. / Lawson, J.D. / Skene, R. / Hoffman, I. / Atienza, J. / Kahana, J. / De Jong, R. / Farrell, P. / Balakrishna, D. / Halkowycz, P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5tc0.cif.gz | 212.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5tc0.ent.gz | 169.5 KB | Display | PDB format |
PDBx/mmJSON format | 5tc0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tc/5tc0 ftp://data.pdbj.org/pub/pdb/validation_reports/tc/5tc0 | HTTPS FTP |
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-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: 0 / Refine code: 0
NCS ensembles :
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-Components
#1: Protein | Mass: 35994.551 Da / Num. of mol.: 2 / Fragment: UNP residues 570-864 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MERTK, MER / Plasmid: pSX71 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) References: UniProt: Q12866, receptor protein-tyrosine kinase #2: Chemical | ChemComp-79Y / | #3: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.2 Å3/Da / Density % sol: 44.03 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.5 / Details: 29% PEG 400, 0.2M MgCl2, 0,1M Tris pH 8.5 |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.9764848 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: May 27, 2010 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: Asymmetric cut single crystal Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9764848 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.24→50 Å / Num. obs: 25183 / % possible obs: 84 % / Redundancy: 4.1 % / Rmerge(I) obs: 0.073 / Net I/av σ(I): 16.622 / Net I/σ(I): 10.1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.24→30 Å / Cor.coef. Fo:Fc: 0.942 / Cor.coef. Fo:Fc free: 0.911 / SU B: 28.687 / SU ML: 0.283 / SU R Cruickshank DPI: 0.3914 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.391 / ESU R Free: 0.259 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 116.72 Å2 / Biso mean: 56.147 Å2 / Biso min: 25.13 Å2
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Refinement step | Cycle: final / Resolution: 2.24→30 Å
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Refine LS restraints |
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Refine LS restraints NCS | Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Weight position: 0.05
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LS refinement shell | Resolution: 2.241→2.299 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Origin x: 18.2682 Å / Origin y: -2.8269 Å / Origin z: 15.8341 Å
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