[English] 日本語
Yorodumi- PDB-6nfh: BTK in complex with inhibitor 8-(2,3-dihydro-1H-inden-5-yl)-2-({4... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6nfh | ||||||
---|---|---|---|---|---|---|---|
Title | BTK in complex with inhibitor 8-(2,3-dihydro-1H-inden-5-yl)-2-({4-[(2S)-3-(dimethylamino)-2-hydroxypropoxy]phenyl}amino)-5,8-dihydropteridine-6,7-dione | ||||||
Components | Tyrosine-protein kinase BTK | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / Bruton Tyrosine kinase / BTK / Kinase / BTK 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) / 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 | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.4 Å | ||||||
Authors | Mirzadegan, T. / Damm-Ganamet, K.L. | ||||||
Citation | Journal: J.Chem.Inf.Model. / Year: 2019 Title: Accelerating Lead Identification by High Throughput Virtual Screening: Prospective Case Studies from the Pharmaceutical Industry. Authors: Damm-Ganamet, K.L. / Arora, N. / Becart, S. / Edwards, J.P. / Lebsack, A.D. / McAllister, H.M. / Nelen, M.I. / Rao, N.L. / Westover, L. / Wiener, J.J.M. / Mirzadegan, T. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 6nfh.cif.gz | 146.6 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6nfh.ent.gz | 112.5 KB | Display | PDB format |
PDBx/mmJSON format | 6nfh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6nfh_validation.pdf.gz | 706.4 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6nfh_full_validation.pdf.gz | 707.9 KB | Display | |
Data in XML | 6nfh_validation.xml.gz | 15.4 KB | Display | |
Data in CIF | 6nfh_validation.cif.gz | 23.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nf/6nfh ftp://data.pdbj.org/pub/pdb/validation_reports/nf/6nfh | HTTPS FTP |
-Related structure data
Related structure data | 6nfiC 1k2pS S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 31598.287 Da / Num. of mol.: 1 / Fragment: kinase domain (UNP residues 389-659) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BTK, AGMX1, ATK, BPK / Production host: Escherichia coli (E. coli) References: UniProt: Q06187, non-specific protein-tyrosine kinase | ||
---|---|---|---|
#2: Chemical | ChemComp-KLM / | ||
#3: Chemical | ChemComp-EDO / #4: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.27 Å3/Da / Density % sol: 45.85 % |
---|---|
Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 6.5 Details: 31% w/v PEG5000 MME, 0.1 M MES, pH 6.5, 0.1 M ammonium sulfate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 0.99987 Å |
Detector | Type: DECTRIS PILATUS 2M-F / Detector: PIXEL / Date: May 14, 2013 |
Radiation | Monochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.99987 Å / Relative weight: 1 |
Reflection | Resolution: 1.4→59.33 Å / Num. obs: 54763 / % possible obs: 95.2 % / Redundancy: 2.3 % / Rrim(I) all: 0.076 / Rsym value: 0.059 / Net I/σ(I): 10 |
Reflection shell | Resolution: 1.4→1.65 Å / Rmerge(I) obs: 0.481 / CC1/2: 0.755 |
-Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB entry 1K2P Resolution: 1.4→59.33 Å / Cor.coef. Fo:Fc: 0.973 / Cor.coef. Fo:Fc free: 0.952 / SU B: 2.868 / SU ML: 0.049 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.074 / ESU R Free: 0.07 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 78.98 Å2 / Biso mean: 14.678 Å2 / Biso min: 6.14 Å2
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.4→59.33 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 1.401→1.438 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
|