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Yorodumi- PDB-5zz4: Crystal structure of bruton's tyrosine kinase in complex with inh... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5zz4 | ||||||
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Title | Crystal structure of bruton's tyrosine kinase in complex with inhibitor 2e | ||||||
Components | Tyrosine-protein kinase BTK | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / protein kinase / inhibitor complex / non-covalent / 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 B cell differentiation / positive regulation of immunoglobulin production / positive regulation of NLRP3 inflammasome complex assembly / negative regulation of interleukin-10 production / phospholipase activator activity / 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 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 / 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 / G beta:gamma signalling through BTK / Regulation of actin dynamics for phagocytic cup formation / 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 / metal ion binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.9 Å | ||||||
Authors | Kawahata, W. / Asami, T. / Irie, T. / Kiyoi, T. / Taniguchi, H. / Asamitsu, Y. / Inoue, T. / Miyake, T. / Sawa, M. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2018 Title: Design and Synthesis of Novel Amino-triazine Analogues as Selective Bruton's Tyrosine Kinase Inhibitors for Treatment of Rheumatoid Arthritis. Authors: Kawahata, W. / Asami, T. / Kiyoi, T. / Irie, T. / Taniguchi, H. / Asamitsu, Y. / Inoue, T. / Miyake, T. / Sawa, M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5zz4.cif.gz | 323.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5zz4.ent.gz | 263.2 KB | Display | PDB format |
PDBx/mmJSON format | 5zz4.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zz/5zz4 ftp://data.pdbj.org/pub/pdb/validation_reports/zz/5zz4 | HTTPS FTP |
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-Related structure data
Related structure data | 3genS 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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3 |
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4 |
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5 |
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6 |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
NCS oper:
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-Components
#1: Protein | Mass: 31178.926 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BTK, AGMX1, ATK, BPK / Production host: unidentified baculovirus References: UniProt: Q06187, non-specific protein-tyrosine kinase #2: Chemical | ChemComp-9M3 / |
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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: 2.34 Å3/Da / Density % sol: 47.36 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7 Details: 0.1M imidazole(pH7.0), 0.1 M Potassium thiocyanate, 30% w/v PEG MME 2000, 4% Polypropylene glycol P 400 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-002 / Wavelength: 1.54 Å |
Detector | Type: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Jul 12, 2012 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54 Å / Relative weight: 1 |
Reflection | Resolution: 2.9→50 Å / Num. obs: 38992 / % possible obs: 100 % / Redundancy: 3.8 % / Rmerge(I) obs: 0.112 / Net I/σ(I): 5.4 |
Reflection shell | Resolution: 2.9→2.95 Å / Rmerge(I) obs: 0.25 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3GEN Resolution: 2.9→48.99 Å / Cor.coef. Fo:Fc: 0.923 / Cor.coef. Fo:Fc free: 0.835 / SU B: 23.697 / SU ML: 0.451 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.55 Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 130.54 Å2 / Biso mean: 48.881 Å2 / Biso min: 16.72 Å2
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Refinement step | Cycle: final / Resolution: 2.9→48.99 Å
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Refine LS restraints |
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Refine LS restraints NCS | Ens-ID: 1 / Refine-ID: X-RAY DIFFRACTION
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LS refinement shell | Resolution: 2.9→2.975 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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