+
Open data
-
Basic information
Entry | Database: PDB / ID: 8bab | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of JAK2 JH2-V617F in complex with CB76 | ||||||
![]() | Tyrosine-protein kinase JAK2 | ||||||
![]() | TRANSFERASE / Janus kinase / pseudokinase / inhibitor complex / JAK2 / JH2 | ||||||
Function / homology | ![]() interleukin-35-mediated signaling pathway / nuclear receptor-mediated mineralocorticoid signaling pathway / histone H3Y41 kinase activity / activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway / positive regulation of growth factor dependent skeletal muscle satellite cell proliferation / symbiont-induced defense-related programmed cell death / mammary gland epithelium development / regulation of postsynapse to nucleus signaling pathway / positive regulation of growth hormone receptor signaling pathway / granulocyte macrophage colony-stimulating factor receptor complex ...interleukin-35-mediated signaling pathway / nuclear receptor-mediated mineralocorticoid signaling pathway / histone H3Y41 kinase activity / activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway / positive regulation of growth factor dependent skeletal muscle satellite cell proliferation / symbiont-induced defense-related programmed cell death / mammary gland epithelium development / regulation of postsynapse to nucleus signaling pathway / positive regulation of growth hormone receptor signaling pathway / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / Signaling by Erythropoietin / collagen-activated signaling pathway / interleukin-12 receptor binding / Erythropoietin activates STAT5 / interleukin-5-mediated signaling pathway / response to interleukin-12 / Erythropoietin activates Phospholipase C gamma (PLCG) / positive regulation of leukocyte proliferation / post-embryonic hemopoiesis / interleukin-12 receptor complex / activation of Janus kinase activity / tyrosine phosphorylation of STAT protein / interleukin-23 receptor complex / positive regulation of MHC class II biosynthetic process / positive regulation of platelet aggregation / Interleukin-23 signaling / type 1 angiotensin receptor binding / positive regulation of T-helper 17 type immune response / positive regulation of platelet activation / acetylcholine receptor binding / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / cellular response to interleukin-3 / interleukin-3-mediated signaling pathway / regulation of nitric oxide biosynthetic process / positive regulation of signaling receptor activity / Signaling by Leptin / Interleukin-12 signaling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / positive regulation of epithelial cell apoptotic process / positive regulation of natural killer cell proliferation / positive regulation of cell-substrate adhesion / regulation of receptor signaling pathway via JAK-STAT / growth hormone receptor binding / response to hydroperoxide / axon regeneration / growth hormone receptor signaling pathway / peptide hormone receptor binding / negative regulation of cardiac muscle cell apoptotic process / intrinsic apoptotic signaling pathway in response to oxidative stress / extrinsic component of plasma membrane / IFNG signaling activates MAPKs / Interleukin-20 family signaling / interleukin-6-mediated signaling pathway / negative regulation of cell-cell adhesion / Interleukin-6 signaling / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / enzyme-linked receptor protein signaling pathway / Prolactin receptor signaling / MAPK3 (ERK1) activation / negative regulation of DNA binding / positive regulation of nitric-oxide synthase biosynthetic process / response to amine / positive regulation of interleukin-17 production / extrinsic component of cytoplasmic side of plasma membrane / MAPK1 (ERK2) activation / mesoderm development / cell surface receptor signaling pathway via JAK-STAT / positive regulation of SMAD protein signal transduction / platelet-derived growth factor receptor signaling pathway / Interleukin-3, Interleukin-5 and GM-CSF signaling / insulin receptor substrate binding / growth hormone receptor signaling pathway via JAK-STAT / response to tumor necrosis factor / Interleukin receptor SHC signaling / post-translational protein modification / cellular response to dexamethasone stimulus / phosphatidylinositol 3-kinase binding / Regulation of IFNG signaling / type II interferon-mediated signaling pathway / Erythropoietin activates RAS / Growth hormone receptor signaling / extrinsic apoptotic signaling pathway / positive regulation of T cell proliferation / Signaling by CSF3 (G-CSF) / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of vascular associated smooth muscle cell proliferation / tumor necrosis factor-mediated signaling pathway / actin filament polymerization / SH2 domain binding / erythrocyte differentiation / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / positive regulation of apoptotic signaling pathway / positive regulation of interleukin-1 beta production / caveola / endosome lumen / positive regulation of cell differentiation Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Haikarainen, T. / Silvennoinen, O. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Identification of Novel Small Molecule Ligands for JAK2 Pseudokinase Domain. Authors: Virtanen, A.T. / Haikarainen, T. / Sampathkumar, P. / Palmroth, M. / Liukkonen, S. / Liu, J. / Nekhotiaeva, N. / Hubbard, S.R. / Silvennoinen, O. | ||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 155.7 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 98.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 718.3 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 719.5 KB | Display | |
Data in XML | ![]() | 15.7 KB | Display | |
Data in CIF | ![]() | 23.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8b8nC ![]() 8b8uC ![]() 8b99C ![]() 8b9eC ![]() 8b9hC ![]() 8ba2C ![]() 8ba3C ![]() 8ba4C ![]() 8bakC ![]() 8ex0C ![]() 8ex1C ![]() 8ex2C ![]() 4fvrS S: Starting model for refinement C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||||||
Unit cell |
|
-
Components
#1: Protein | Mass: 33284.133 Da / Num. of mol.: 1 / Mutation: W777A, F794H, V617F Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: O60674, non-specific protein-tyrosine kinase | ||||||
---|---|---|---|---|---|---|---|
#2: Chemical | ChemComp-GOL / #3: Chemical | ChemComp-Q8N / | #4: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|
-
Sample preparation
Crystal | Density Matthews: 2.61 Å3/Da / Density % sol: 52.82 % |
---|---|
Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 8 / Details: 0.1M Tris pH 8, 20% PEG4000, 0.2M Na-acetate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Nov 24, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97625 Å / Relative weight: 1 |
Reflection | Resolution: 1.55→57.378 Å / Num. obs: 97536 / % possible obs: 99.9 % / Redundancy: 7.1 % / Biso Wilson estimate: 20.79 Å2 / CC1/2: 0.999 / Net I/σ(I): 11.93 |
Reflection shell | Resolution: 1.55→1.64 Å / Redundancy: 6.9 % / Mean I/σ(I) obs: 1.42 / Num. unique obs: 15650 / CC1/2: 0.638 / % possible all: 99.2 |
-
Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: ![]() Starting model: 4fvr Resolution: 1.55→40.37 Å / SU ML: 0.1815 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 21.4047 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 30.33 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.55→40.37 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
|