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Yorodumi- PDB-5k0k: Crystal structure of the catalytic domain of the proto-oncogene t... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5k0k | ||||||
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Title | Crystal structure of the catalytic domain of the proto-oncogene tyrosine-protein kinase MER in complex with inhibitor UNC2434 | ||||||
Components | Tyrosine-protein kinase Mer | ||||||
Keywords | Transferase/Transferase Inhibitor / Macrocyclic / Pyrrolopyrimidines / Drug Design / Fibrinolytic Agents / Protein Kinase Inhibitors / Proto-Oncogene Proteins / Pyrimidines / Receptor Protein-Tyrosine Kinases / Structure-Activity Relationship / Thrombosis / 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 / transmembrane receptor protein tyrosine kinase activity / 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 / transmembrane receptor protein tyrosine kinase activity / phagocytosis / positive regulation of phagocytosis / substrate adhesion-dependent cell spreading / establishment of localization in cell / receptor protein-tyrosine kinase / Cell surface interactions at the vascular wall / platelet activation / cell migration / cell-cell signaling / retina development in camera-type eye / nervous system development / spermatogenesis / receptor complex / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cell surface receptor signaling pathway / 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: 2.545 Å | ||||||
Authors | Wang, X. / Liu, J. / Zhang, W. / Stashko, M.A. / Nichols, J. / DeRyckere, D. / Miley, M.J. / Norris-Drouin, J. / Chen, Z. / Machius, M. ...Wang, X. / Liu, J. / Zhang, W. / Stashko, M.A. / Nichols, J. / DeRyckere, D. / Miley, M.J. / Norris-Drouin, J. / Chen, Z. / Machius, M. / Wood, E. / Graham, D.K. / Earp, H.S. / Graham, K. / Kireev, D. / Frye, S.V. | ||||||
Citation | Journal: ACS Med Chem Lett / Year: 2016 Title: Design and Synthesis of Novel Macrocyclic Mer Tyrosine Kinase Inhibitors. Authors: Wang, X. / Liu, J. / Zhang, W. / Stashko, M.A. / Nichols, J. / Miley, M.J. / Norris-Drouin, J. / Chen, Z. / Machius, M. / DeRyckere, D. / Wood, E. / Graham, D.K. / Earp, H.S. / Kireev, D. / Frye, S.V. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5k0k.cif.gz | 316.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5k0k.ent.gz | 262.1 KB | Display | PDB format |
PDBx/mmJSON format | 5k0k.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5k0k_validation.pdf.gz | 906.3 KB | Display | wwPDB validaton report |
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Full document | 5k0k_full_validation.pdf.gz | 914.2 KB | Display | |
Data in XML | 5k0k_validation.xml.gz | 20.9 KB | Display | |
Data in CIF | 5k0k_validation.cif.gz | 27.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k0/5k0k ftp://data.pdbj.org/pub/pdb/validation_reports/k0/5k0k | HTTPS FTP |
-Related structure data
Related structure data | 3brbS S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 35889.434 Da / Num. of mol.: 2 / Fragment: catalytic domain, UNP residues 570-864 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MERTK, MER / Production host: Escherichia coli (E. coli) References: UniProt: Q12866, receptor protein-tyrosine kinase #2: Chemical | ChemComp-CL / #3: Chemical | #4: Chemical | ChemComp-MG / | #5: 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: 2.21 Å3/Da / Density % sol: 44.37 % |
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Crystal grow | Temperature: 285.2 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: Protein at 32.5 mg/mL (in 20 mM Tris pH 8.0, 500 mM NaCl, 2mM BME) was incubated overnight with inhibitor at 2.5 mM final concentration, and then was mixed 1:1 with crystallization solution ...Details: Protein at 32.5 mg/mL (in 20 mM Tris pH 8.0, 500 mM NaCl, 2mM BME) was incubated overnight with inhibitor at 2.5 mM final concentration, and then was mixed 1:1 with crystallization solution (27-33% (v/v) Peg 400, 200 mM MgCl2, 100 mM Tris pH 8.5). |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-BM / Wavelength: 0.9792 Å |
Detector | Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Dec 12, 2012 |
Radiation | Monochromator: Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9792 Å / Relative weight: 1 |
Reflection | Resolution: 2.545→34.55 Å / Num. obs: 20516 / % possible obs: 99.8 % / Observed criterion σ(F): -3 / Observed criterion σ(I): -3 / Redundancy: 4.2 % / Biso Wilson estimate: 35.7 Å2 / Rmerge(I) obs: 0.086 / Net I/σ(I): 7.9 |
Reflection shell | Resolution: 2.545→2.57 Å / Redundancy: 3.8 % / Rmerge(I) obs: 0.686 / Mean I/σ(I) obs: 1.9 / % possible all: 96 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3BRB Resolution: 2.545→34.547 Å / SU ML: 0.31 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 26.97
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 209.51 Å2 / Biso mean: 56.6 Å2 / Biso min: 20.53 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.545→34.547 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 13
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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