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Open data
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Basic information
Entry | Database: PDB / ID: 7n4s | ||||||
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Title | Bruton's tyrosine kinase in complex with compound 65 | ||||||
![]() | Tyrosine-protein kinase BTK | ||||||
![]() | TRANSFERASE/TRANSFERASE INHIBITOR / transferase / transferase inhibitor / kinase / kinase inhibitor / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||
Function / homology | ![]() 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 / calcium-mediated signaling / apoptotic signaling pathway / FCGR3A-mediated phagocytosis / B cell receptor signaling pathway / non-specific protein-tyrosine kinase / 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 / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() | ||||||
![]() | Metrick, C.M. / Marcotte, D.J. | ||||||
![]() | ![]() Title: Utilizing structure based drug design and metabolic soft spot identification to optimize the in vitro potency and in vivo pharmacokinetic properties leading to the discovery of novel ...Title: Utilizing structure based drug design and metabolic soft spot identification to optimize the in vitro potency and in vivo pharmacokinetic properties leading to the discovery of novel reversible Bruton's tyrosine kinase inhibitors. Authors: Hopkins, B.T. / Bame, E. / Bell, N. / Bohnert, T. / Bowden-Verhoek, J.K. / Bui, M. / Cancilla, M.T. / Conlon, P. / Cullen, P. / Erlanson, D.A. / Fan, J. / Fuchs-Knotts, T. / Hansen, S. / ...Authors: Hopkins, B.T. / Bame, E. / Bell, N. / Bohnert, T. / Bowden-Verhoek, J.K. / Bui, M. / Cancilla, M.T. / Conlon, P. / Cullen, P. / Erlanson, D.A. / Fan, J. / Fuchs-Knotts, T. / Hansen, S. / Heumann, S. / Jenkins, T.J. / Gua, C. / Liu, Y. / Liu, Y. / Lulla, M. / Marcotte, D. / Marx, I. / McDowell, B. / Mertsching, E. / Negrou, E. / Romanowski, M.J. / Scott, D. / Silvian, L. / Yang, W. / Zhong, M. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 81 KB | Display | ![]() |
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PDB format | ![]() | 47.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 759.7 KB | Display | ![]() |
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Full document | ![]() | 760.9 KB | Display | |
Data in XML | ![]() | 11.5 KB | Display | |
Data in CIF | ![]() | 15 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7n4qC ![]() 7n4rC ![]() 5p9jS C: citing same article ( S: Starting model for refinement |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 31428.078 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q06187, non-specific protein-tyrosine kinase |
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#2: Chemical | ChemComp-0B0 / ( |
#3: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.28 Å3/Da / Density % sol: 46.04 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion Details: 0.1M BisTRIS pH 6.5, 0.2M Ammonium Acetate, 0.1M Guanidine HCl, 20% PEG2200 MME |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() |
Detector | Type: RIGAKU / Detector: CCD / Date: Jun 11, 2008 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.05→50 Å / Num. obs: 30368 / % possible obs: 87.9 % / Redundancy: 1.5 % / Biso Wilson estimate: 31.74 Å2 / Rmerge(I) obs: 0.116 / Net I/σ(I): 10.2 |
Reflection shell | Resolution: 2.05→2.12 Å / Rmerge(I) obs: 0.553 / Num. unique obs: 2909 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 5p9j Resolution: 2.05→32.03 Å / SU ML: 0.2589 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 29.5154 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 34.09 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.05→32.03 Å
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Refine LS restraints |
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LS refinement shell |
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