+Open data
-Basic information
Entry | Database: PDB / ID: 6vxq | ||||||
---|---|---|---|---|---|---|---|
Title | Bruton's tyrosine kinase in complex with compound 5 | ||||||
Components | Tyrosine-protein kinase BTK | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / kinase / 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) / 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 / negative regulation of B cell proliferation / Fc-epsilon receptor signaling pathway / B cell activation / 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 / 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 / positive regulation of interleukin-6 production / cellular response to reactive oxygen species / peptidyl-tyrosine phosphorylation / 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 / 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 | Metrick, C.M. / Marcotte, D.J. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2020 Title: Discovery of BIIB068: A Selective, Potent, Reversible Bruton's Tyrosine Kinase Inhibitor as an Orally Efficacious Agent for Autoimmune Diseases. Authors: Ma, B. / Bohnert, T. / Otipoby, K.L. / Tien, E. / Arefayene, M. / Bai, J. / Bajrami, B. / Bame, E. / Chan, T.R. / Humora, M. / MacPhee, J.M. / Marcotte, D. / Mehta, D. / Metrick, C.M. / ...Authors: Ma, B. / Bohnert, T. / Otipoby, K.L. / Tien, E. / Arefayene, M. / Bai, J. / Bajrami, B. / Bame, E. / Chan, T.R. / Humora, M. / MacPhee, J.M. / Marcotte, D. / Mehta, D. / Metrick, C.M. / Moniz, G. / Polack, E. / Poreci, U. / Prefontaine, A. / Sheikh, S. / Schroeder, P. / Smirnakis, K. / Zhang, L. / Zheng, F. / Hopkins, B.T. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 6vxq.cif.gz | 149.1 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6vxq.ent.gz | 95.3 KB | Display | PDB format |
PDBx/mmJSON format | 6vxq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6vxq_validation.pdf.gz | 334 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 6vxq_full_validation.pdf.gz | 334 KB | Display | |
Data in XML | 6vxq_validation.xml.gz | 1.3 KB | Display | |
Data in CIF | 6vxq_validation.cif.gz | 5.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vx/6vxq ftp://data.pdbj.org/pub/pdb/validation_reports/vx/6vxq | HTTPS FTP |
-Related structure data
Related structure data | 6w06C 6w07C 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: 33896.859 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 | ||||||
---|---|---|---|---|---|---|---|
#2: Chemical | #3: Chemical | ChemComp-RQS / | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.12 Å3/Da / Density % sol: 42.05 % |
---|---|
Crystal grow | Temperature: 277 K / Method: vapor diffusion / Details: bis-tris, ammonium salt, PEG |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.98 Å |
Detector | Type: RAYONIX MX-225 / Detector: CCD / Date: Mar 6, 2008 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 1.31→16.69 Å / Num. obs: 67678 / % possible obs: 97.3 % / Redundancy: 7 % / Biso Wilson estimate: 11.43 Å2 / Rmerge(I) obs: 0.091 / Net I/σ(I): 10.3 |
Reflection shell | Resolution: 1.31→1.39 Å / Redundancy: 6.5 % / Rmerge(I) obs: 0.968 / Mean I/σ(I) obs: 2.4 / Num. unique obs: 9185 / % possible all: 92 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1K2P Resolution: 1.4→16.69 Å / SU ML: 0.114 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 18.7373
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 15.63 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.4→16.69 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
|