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Yorodumi- PDB-6yyk: Crystal Structure of 1,5-dimethylindoline-2,3-dione covalently bo... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6yyk | ||||||
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Title | Crystal Structure of 1,5-dimethylindoline-2,3-dione covalently bound to the PH domain of Bruton's tyrosine kinase mutant R28C | ||||||
Components | Tyrosine-protein kinase BTK | ||||||
Keywords | TRANSFERASE / BTK / Covalent fragments / surface entrophy reduction / crystal engineering | ||||||
Function / homology | Function and homology information regulation of B cell cytokine production / proteoglycan catabolic process / monocyte proliferation / positive regulation of interleukin-17A production / regulation of B cell apoptotic process / eosinophil homeostasis / positive regulation of type III hypersensitivity / B cell affinity maturation / positive regulation of synoviocyte proliferation / histamine secretion by mast cell ...regulation of B cell cytokine production / proteoglycan catabolic process / monocyte proliferation / positive regulation of interleukin-17A production / regulation of B cell apoptotic process / eosinophil homeostasis / positive regulation of type III hypersensitivity / B cell affinity maturation / positive regulation of synoviocyte proliferation / histamine secretion by mast cell / neutrophil homeostasis / cellular response to molecule of fungal origin / positive regulation of type I hypersensitivity / cellular response to interleukin-7 / MyD88 deficiency (TLR2/4) / MyD88-dependent toll-like receptor signaling pathway / IRAK4 deficiency (TLR2/4) / positive regulation of immunoglobulin production / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / positive regulation of B cell differentiation / positive regulation of NLRP3 inflammasome complex assembly / phospholipase activator activity / negative regulation of interleukin-10 production / B cell activation / negative regulation of B cell proliferation / Fc-epsilon receptor signaling pathway / mesoderm development / phosphatidylinositol-3,4,5-trisphosphate binding / phospholipase binding / RHO GTPases Activate WASPs and WAVEs / positive regulation of B cell proliferation / positive regulation of phagocytosis / cell maturation / FCERI mediated Ca+2 mobilization / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / apoptotic signaling pathway / FCGR3A-mediated phagocytosis / B cell receptor signaling pathway / non-specific protein-tyrosine kinase / calcium-mediated signaling / non-membrane spanning protein tyrosine kinase activity / Regulation of actin dynamics for phagocytic cup formation / G beta:gamma signalling through BTK / cellular response to reactive oxygen species / peptidyl-tyrosine phosphorylation / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / G alpha (12/13) signalling events / DAP12 signaling / positive regulation of NF-kappaB transcription factor activity / T cell receptor signaling pathway / ER-Phagosome pathway / cytoplasmic vesicle / G alpha (q) signalling events / protein tyrosine kinase activity / adaptive immune response / Potential therapeutics for SARS / response to lipopolysaccharide / intracellular signal transduction / membrane raft / protein phosphorylation / innate immune response / perinuclear region of cytoplasm / ATP binding / identical protein binding / nucleus / metal ion binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.04 Å | ||||||
Authors | Brear, P. / Wagstaff, J. / Hyvonen, M. | ||||||
Funding support | United Kingdom, 1items
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Citation | Journal: To Be Published Title: Optimising crystallographic systems for structure-guided drug discovery Authors: Brear, P. / Fischer, G. / May, M. / Pantelejevs, T. / Mathieu, R. / Rossmann, M. / Wagstaff, J. / Blaszczyk, B. / Hyvonen, M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6yyk.cif.gz | 81.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6yyk.ent.gz | 60 KB | Display | PDB format |
PDBx/mmJSON format | 6yyk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yy/6yyk ftp://data.pdbj.org/pub/pdb/validation_reports/yy/6yyk | HTTPS FTP |
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-Related structure data
Related structure data | 6xufC 6xujC 6yyfC 6yygC 1btkS S: Starting model for refinement C: citing same article (ref.) |
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Similar 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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-Components
#1: Protein | Mass: 19928.963 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BTK, AGMX1, ATK, BPK / Plasmid: pBAT4 / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: Q06187, non-specific protein-tyrosine kinase #2: Chemical | #3: Chemical | #4: Chemical | ChemComp-IS7 / | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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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: 2.1 Å3/Da / Density % sol: 41.55 % / Mosaicity: 0 ° |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: 0.1 M TRIS 8.5 pH, 32.5% w/v PEG 3350, 200mM MgCl2 500 mM NaCl |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9795 Å | |||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 3, 2017 | |||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 | |||||||||||||||||||||||||||
Reflection | Resolution: 2.04→60.41 Å / Num. obs: 21231 / % possible obs: 99.8 % / Redundancy: 3.2 % / CC1/2: 0.996 / Rmerge(I) obs: 0.074 / Rpim(I) all: 0.049 / Rrim(I) all: 0.09 / Net I/σ(I): 5.3 / Num. measured all: 67401 / Scaling rejects: 11 | |||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Redundancy: 3 %
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1BTK Resolution: 2.04→57.74 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.931 / SU B: 15.021 / SU ML: 0.333 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.259 / ESU R Free: 0.228 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 203.38 Å2 / Biso mean: 67.47 Å2 / Biso min: 36.46 Å2
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Refinement step | Cycle: final / Resolution: 2.04→57.74 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.04→2.089 Å / Rfactor Rfree error: 0
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