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Yorodumi- PDB-5k0x: Crystal structure of the catalytic domain of the proto-oncogene t... -
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-Basic information
Entry | Database: PDB / ID: 5k0x | ||||||
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Title | Crystal structure of the catalytic domain of the proto-oncogene tyrosine-protein kinase MER in complex with inhibitor UNC2541 | ||||||
Components | Tyrosine-protein kinase Mer | ||||||
Keywords | Transferase/Transferase Inhibitor / Macrocyclic / 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 / 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: 2.231 Å | ||||||
Authors | McIver, A.L. / Zhang, W. / Liu, Q. / Jiang, X. / Stashko, M.A. / Nichols, J. / Miley, M.J. / Norris-Drouin, J. / Machius, M. / DeRyckere, D. ...McIver, A.L. / Zhang, W. / Liu, Q. / Jiang, X. / Stashko, M.A. / Nichols, J. / Miley, M.J. / Norris-Drouin, J. / Machius, M. / DeRyckere, D. / Wood, E. / Graham, D.K. / Earp, H.S. / Kireev, D. / Frye, S.V. / Wang, X. | ||||||
Citation | Journal: ChemMedChem / Year: 2017 Title: Discovery of Macrocyclic Pyrimidines as MerTK-Specific Inhibitors. Authors: McIver, A.L. / Zhang, W. / Liu, Q. / Jiang, X. / Stashko, M.A. / Nichols, J. / Miley, M.J. / Norris-Drouin, J. / Machius, M. / DeRyckere, D. / Wood, E. / Graham, D.K. / Earp, H.S. / Kireev, ...Authors: McIver, A.L. / Zhang, W. / Liu, Q. / Jiang, X. / Stashko, M.A. / Nichols, J. / Miley, M.J. / Norris-Drouin, J. / Machius, M. / DeRyckere, D. / Wood, E. / Graham, D.K. / Earp, H.S. / Kireev, D. / Frye, S.V. / Wang, X. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5k0x.cif.gz | 213.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5k0x.ent.gz | 171.9 KB | Display | PDB format |
PDBx/mmJSON format | 5k0x.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/k0/5k0x ftp://data.pdbj.org/pub/pdb/validation_reports/k0/5k0x | HTTPS FTP |
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-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: 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: 2.25 Å3/Da / Density % sol: 45.26 % |
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Crystal grow | Temperature: 286 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: 1 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: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.23→50 Å / Num. obs: 30743 / % possible obs: 99.9 % / Observed criterion σ(F): -3 / Observed criterion σ(I): -3 / Redundancy: 4.2 % / Biso Wilson estimate: 29.5 Å2 / Rmerge(I) obs: 0.076 / Net I/σ(I): 8.8 |
Reflection shell | Resolution: 2.23→2.27 Å / Redundancy: 4 % / Rmerge(I) obs: 0.661 / Mean I/σ(I) obs: 2 / % possible all: 99 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3BRB Resolution: 2.231→27.864 Å / SU ML: 0.23 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 26.63
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 178.81 Å2 / Biso mean: 48.6854 Å2 / Biso min: 5.37 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.231→27.864 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: 14
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