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Yorodumi- PDB-8ex2: Crystal structure of JAK2 JH2 (pseudokinase domain) in complex wi... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8ex2 | ||||||
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Title | Crystal structure of JAK2 JH2 (pseudokinase domain) in complex with HTSA3 | ||||||
Components | Tyrosine-protein kinase JAK2 | ||||||
Keywords | TRANSFERASE / JANUS TYROSINE KINASE / JAK2 / PSEUDOKINASE / PHOSPHORYLATION | ||||||
Function / homology | Function and homology information 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 / erythropoietin-mediated signaling pathway ...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 / erythropoietin-mediated signaling pathway / interleukin-23-mediated 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 platelet aggregation / positive regulation of MHC class II biosynthetic process / Interleukin-23 signaling / positive regulation of T-helper 17 type immune response / positive regulation of platelet activation / acetylcholine receptor binding / interleukin-12-mediated signaling pathway / type 1 angiotensin receptor binding / positive regulation of NK T cell proliferation / interleukin-3-mediated signaling pathway / cellular response to interleukin-3 / regulation of nitric oxide biosynthetic process / Signaling by Leptin / Interleukin-12 signaling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / positive regulation of signaling receptor activity / 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 / negative regulation of cardiac muscle cell apoptotic process / intrinsic apoptotic signaling pathway in response to oxidative stress / peptide hormone receptor binding / extrinsic component of plasma membrane / IFNG signaling activates MAPKs / Interleukin-20 family signaling / negative regulation of cell-cell adhesion / Interleukin-6 signaling / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / interleukin-6-mediated signaling pathway / enzyme-linked receptor protein signaling pathway / Prolactin receptor signaling / MAPK3 (ERK1) activation / negative regulation of DNA binding / positive regulation of interleukin-17 production / positive regulation of nitric-oxide synthase biosynthetic process / response to amine / extrinsic component of cytoplasmic side of plasma membrane / MAPK1 (ERK2) activation / mesoderm development / positive regulation of SMAD protein signal transduction / cell surface receptor signaling pathway via JAK-STAT / platelet-derived growth factor receptor signaling pathway / insulin receptor substrate binding / Interleukin-3, Interleukin-5 and GM-CSF signaling / response to tumor necrosis factor / growth hormone receptor signaling pathway via JAK-STAT / Interleukin receptor SHC signaling / phosphatidylinositol 3-kinase binding / type II interferon-mediated signaling pathway / Regulation of IFNG signaling / positive regulation of T cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / Erythropoietin activates RAS / Growth hormone receptor signaling / extrinsic apoptotic signaling pathway / Signaling by CSF3 (G-CSF) / tumor necrosis factor-mediated signaling pathway / positive regulation of vascular associated smooth muscle cell proliferation / actin filament polymerization / SH2 domain binding / cellular response to dexamethasone stimulus / post-translational protein modification / erythrocyte differentiation / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / positive regulation of interleukin-1 beta production / endosome lumen / positive regulation of cell differentiation Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å | ||||||
Authors | Sampathkumar, P. / Hubbard, S.R. | ||||||
Funding support | United States, 1items
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Citation | Journal: Pharmaceuticals / Year: 2023 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 |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ex2.cif.gz | 149.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ex2.ent.gz | 93.6 KB | Display | PDB format |
PDBx/mmJSON format | 8ex2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ex2_validation.pdf.gz | 748.7 KB | Display | wwPDB validaton report |
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Full document | 8ex2_full_validation.pdf.gz | 751 KB | Display | |
Data in XML | 8ex2_validation.xml.gz | 15 KB | Display | |
Data in CIF | 8ex2_validation.cif.gz | 21.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ex/8ex2 ftp://data.pdbj.org/pub/pdb/validation_reports/ex/8ex2 | HTTPS FTP |
-Related structure data
Related structure data | 8b8nC 8b8uC 8b99C 8b9eC 8b9hC 8ba2C 8ba3C 8ba4C 8babC 8bakC 8ex0C 8ex1C 4fvqS S: Starting model for refinement C: citing same article (ref.) |
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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: 33121.945 Da / Num. of mol.: 1 / Mutation: W659A, W777A, F794H Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: JAK2 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O60674, non-specific protein-tyrosine kinase | ||||
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#2: Chemical | ChemComp-Q2Q / | ||||
#3: Chemical | #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: 2.56 Å3/Da / Density % sol: 51.89 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: HEPES, PEG 10K |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 19-BM / Wavelength: 0.9792 Å |
Detector | Type: ADSC QUANTUM 210r / Detector: CCD / Date: Feb 24, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9792 Å / Relative weight: 1 |
Reflection | Resolution: 1.9→27.02 Å / Num. obs: 25094 / % possible obs: 99.8 % / Redundancy: 4.5 % / Biso Wilson estimate: 18.59 Å2 / Rmerge(I) obs: 0.087 / Net I/σ(I): 12.1 |
Reflection shell | Resolution: 1.9→1.93 Å / Redundancy: 4.4 % / Rmerge(I) obs: 0.629 / Num. unique obs: 1248 / CC1/2: 0.88 / CC star: 0.968 / % possible all: 99.8 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4FVQ Resolution: 1.9→27.02 Å / SU ML: 0.1763 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 21.0593 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: 24.71 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.9→27.02 Å
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Refine LS restraints |
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LS refinement shell |
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