+Open data
-Basic information
Entry | Database: PDB / ID: 7yc9 | ||||||
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Title | Co-crystal structure of BTK kinase domain with inhibitor | ||||||
Components | Tyrosine-protein kinase BTK | ||||||
Keywords | ANTITUMOR PROTEIN / kinase / 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) / 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 / Resolution: 1.4 Å | ||||||
Authors | Zhou, X. | ||||||
Funding support | 1items
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Citation | Journal: J.Med.Chem. / Year: 2023 Title: Discovery of BGB-8035, a Highly Selective Covalent Inhibitor of Bruton's Tyrosine Kinase for B-Cell Malignancies and Autoimmune Diseases. Authors: Guo, Y. / Hu, N. / Liu, Y. / Zhang, W. / Yu, D. / Shi, G. / Zhang, B. / Yin, L. / Wei, M. / Yuan, X. / Luo, L. / Wang, F. / Song, X. / Xin, L. / Wei, Q. / Li, Y. / Guo, Y. / Chen, S. / ...Authors: Guo, Y. / Hu, N. / Liu, Y. / Zhang, W. / Yu, D. / Shi, G. / Zhang, B. / Yin, L. / Wei, M. / Yuan, X. / Luo, L. / Wang, F. / Song, X. / Xin, L. / Wei, Q. / Li, Y. / Guo, Y. / Chen, S. / Zhang, T. / Zhang, S. / Zhou, X. / Zhang, C. / Su, D. / Liu, J. / Cheng, Z. / Zhang, J. / Xing, H. / Sun, H. / Li, X. / Zhao, Y. / He, M. / Wu, Y. / Guo, Y. / Sun, X. / Tian, A. / Zhou, C. / Young, S. / Liu, X. / Wang, L. / Wang, Z. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7yc9.cif.gz | 83.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7yc9.ent.gz | 57.3 KB | Display | PDB format |
PDBx/mmJSON format | 7yc9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yc/7yc9 ftp://data.pdbj.org/pub/pdb/validation_reports/yc/7yc9 | HTTPS FTP |
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-Related structure data
Related structure data | 6j6mS S: Starting model for refinement |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 31351.984 Da / Num. of mol.: 1 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-IS4 / ( |
#3: Chemical | ChemComp-EDO / |
#4: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.35 Å3/Da / Density % sol: 47.71 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop Details: 0.1M Sodium cacodylate trihydrate pH 7.0, 0.2M Ammonium sulfate, 26% PEG8000 |
-Data collection
Diffraction | Mean temperature: 93 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SPring-8 / Beamline: BL45XU / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Apr 23, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.4→47.63 Å / Num. obs: 58704 / % possible obs: 99.5 % / Redundancy: 4.3 % / CC1/2: 0.998 / Net I/σ(I): 16.1 |
Reflection shell | Resolution: 1.4→1.43 Å / Num. unique obs: 3040 / CC1/2: 0.95 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6J6M Resolution: 1.4→46.47 Å / SU ML: 0.1361 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 16.7219 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: 13.88 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.4→46.47 Å
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Refine LS restraints |
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LS refinement shell |
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