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Yorodumi- PDB-4ot5: Crystal structure of BTK kinase domain complexed with 4-tert-Buty... -
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-Basic information
Entry | Database: PDB / ID: 4ot5 | ||||||
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Title | Crystal structure of BTK kinase domain complexed with 4-tert-Butyl-N-(3-{8-[4-(4-methyl-piperazine-1-carbonyl)-phenylamino]-imidazo[1,2-a]pyrazin-6-yl}-phenyl)-benzamide | ||||||
Components | Tyrosine-protein kinase BTK | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
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) / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / positive regulation of immunoglobulin production / positive regulation of B cell differentiation / positive regulation of NLRP3 inflammasome complex assembly / phospholipase activator activity / negative regulation of interleukin-10 production / negative regulation of B cell proliferation / mesoderm development / Fc-epsilon receptor signaling pathway / B cell activation / phosphatidylinositol-3,4,5-trisphosphate binding / phospholipase binding / RHO GTPases Activate WASPs and WAVEs / positive regulation of phagocytosis / positive regulation of B cell proliferation / cell maturation / FCERI mediated Ca+2 mobilization / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / apoptotic signaling pathway / non-specific protein-tyrosine kinase / FCGR3A-mediated phagocytosis / B cell receptor signaling pathway / non-membrane spanning protein tyrosine kinase activity / calcium-mediated signaling / Regulation of actin dynamics for phagocytic cup formation / peptidyl-tyrosine phosphorylation / G beta:gamma signalling through BTK / positive regulation of interleukin-6 production / cellular response to reactive oxygen species / 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 / protein tyrosine kinase activity / G alpha (q) signalling events / adaptive immune response / response to lipopolysaccharide / Potential therapeutics for SARS / intracellular signal transduction / protein phosphorylation / membrane raft / 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 / FOURIER SYNTHESIS / Resolution: 1.55 Å | ||||||
Authors | Kuglstatter, A. / Wong, A. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2015 Title: Structure-Based Drug Design of RN486, a Potent and Selective Bruton's Tyrosine Kinase (BTK) Inhibitor, for the Treatment of Rheumatoid Arthritis. Authors: Lou, Y. / Han, X. / Kuglstatter, A. / Kondru, R.K. / Sweeney, Z.K. / Soth, M. / McIntosh, J. / Litman, R. / Suh, J. / Kocer, B. / Davis, D. / Park, J. / Frauchiger, S. / Dewdney, N. / Zecic, ...Authors: Lou, Y. / Han, X. / Kuglstatter, A. / Kondru, R.K. / Sweeney, Z.K. / Soth, M. / McIntosh, J. / Litman, R. / Suh, J. / Kocer, B. / Davis, D. / Park, J. / Frauchiger, S. / Dewdney, N. / Zecic, H. / Taygerly, J.P. / Sarma, K. / Hong, J. / Hill, R.J. / Gabriel, T. / Goldstein, D.M. / Owens, T.D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4ot5.cif.gz | 138.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4ot5.ent.gz | 106.3 KB | Display | PDB format |
PDBx/mmJSON format | 4ot5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4ot5_validation.pdf.gz | 675 KB | Display | wwPDB validaton report |
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Full document | 4ot5_full_validation.pdf.gz | 676.3 KB | Display | |
Data in XML | 4ot5_validation.xml.gz | 15.3 KB | Display | |
Data in CIF | 4ot5_validation.cif.gz | 23.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ot/4ot5 ftp://data.pdbj.org/pub/pdb/validation_reports/ot/4ot5 | HTTPS FTP |
-Related structure data
Related structure data | 4ot6C 4otqC 4otrC 3pixS 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: 32521.135 Da / Num. of mol.: 1 / Fragment: UNP residues 378-659 / Mutation: M489A, R492A, E624A, K625A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BTK, AGMX1, ATK, BPK / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q06187, non-specific protein-tyrosine kinase | ||
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#2: Chemical | ChemComp-481 / | ||
#3: Chemical | #4: Water | ChemComp-HOH / | |
-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: 45.23 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8 Details: 33% PEG3350, 0.1 M HEPES, pH 8.0, VAPOR DIFFUSION, HANGING DROP, temperature 293K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD |
Radiation | Monochromator: Liquid Nitrogen cooled Dual Crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.55→40 Å / Num. obs: 42617 / % possible obs: 98.4 % / Redundancy: 4.9 % / Biso Wilson estimate: 19.8 Å2 / Rsym value: 0.078 / Net I/σ(I): 16.4 |
Reflection shell | Resolution: 1.55→1.59 Å / Redundancy: 3.2 % / Mean I/σ(I) obs: 2.6 / Num. unique all: 2705 / Rsym value: 0.381 / % possible all: 85.2 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: PDB ENTRY 3PIX Resolution: 1.55→38.38 Å / Cor.coef. Fo:Fc: 0.972 / Cor.coef. Fo:Fc free: 0.954 / SU B: 2.77 / SU ML: 0.045 / Cross valid method: THROUGHOUT / ESU R: 0.083 / ESU R Free: 0.076 / Stereochemistry target values: MAXIMUM LIKELIHOOD
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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 mean: 23.188 Å2
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Refinement step | Cycle: LAST / Resolution: 1.55→38.38 Å
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