+Open data
-Basic information
Entry | Database: PDB / ID: 8bm2 | ||||||
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Title | Crystal structure of JAK2 JH1 in complex with gandotinib | ||||||
Components | Tyrosine-protein kinase JAK2 | ||||||
Keywords | TRANSFERASE / Janus kinase / inhibitor complex / JAK2 / JH1 | ||||||
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 / 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 / Signaling by Leptin / regulation of nitric oxide biosynthetic process / positive regulation of signaling receptor activity / Interleukin-12 signaling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / positive regulation of epithelial cell apoptotic process / response to hydroperoxide / 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 / 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 / response to amine / positive regulation of interleukin-17 production / negative regulation of DNA binding / positive regulation of nitric-oxide synthase biosynthetic process / 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 / insulin receptor substrate binding / Interleukin-3, Interleukin-5 and GM-CSF signaling / growth hormone receptor signaling pathway via JAK-STAT / response to tumor necrosis factor / Interleukin receptor SHC signaling / 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 / extrinsic component of cytoplasmic side of plasma membrane / positive regulation of vascular associated smooth muscle cell proliferation / tumor necrosis factor-mediated signaling pathway / actin filament polymerization / SH2 domain binding / cellular response to dexamethasone stimulus / erythrocyte differentiation / post-translational protein modification / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / positive regulation of interleukin-1 beta production / caveola / endosome lumen / positive regulation of cell differentiation / positive regulation of apoptotic signaling pathway Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.5 Å | ||||||
Authors | Miao, Y. / Haikarainen, T. | ||||||
Funding support | Finland, 1items
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Citation | Journal: J.Med.Chem. / Year: 2024 Title: Functional and Structural Characterization of Clinical-Stage Janus Kinase 2 Inhibitors Identifies Determinants for Drug Selectivity. Authors: Miao, Y. / Virtanen, A. / Zmajkovic, J. / Hilpert, M. / Skoda, R.C. / Silvennoinen, O. / Haikarainen, T. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8bm2.cif.gz | 319 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8bm2.ent.gz | 211.5 KB | Display | PDB format |
PDBx/mmJSON format | 8bm2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8bm2_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8bm2_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8bm2_validation.xml.gz | 29.7 KB | Display | |
Data in CIF | 8bm2_validation.cif.gz | 44.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bm/8bm2 ftp://data.pdbj.org/pub/pdb/validation_reports/bm/8bm2 | HTTPS FTP |
-Related structure data
Related structure data | 8bpvC 8bpwC 8bx6C 8bx9C 8bxcC 8bxhC 6vn8S 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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2 |
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Unit cell |
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Components on special symmetry positions |
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-Components
#1: Protein | Mass: 37325.336 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: JAK2 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: O60674, non-specific protein-tyrosine kinase #2: Chemical | #3: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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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: 2.53 Å3/Da / Density % sol: 51.31 % |
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Crystal grow | Temperature: 295 K / Method: vapor diffusion, hanging drop / pH: 8.2 / Details: 1.7 M Na-malonate, 0.1 M Gly-Gly pH 8.2 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97625 Å |
Detector | Type: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Nov 29, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97625 Å / Relative weight: 1 |
Reflection | Resolution: 1.5→79.4 Å / Num. obs: 118979 / % possible obs: 100 % / Redundancy: 6.9 % / Biso Wilson estimate: 17.8 Å2 / CC1/2: 0.999 / Net I/σ(I): 12.7 |
Reflection shell | Resolution: 1.5→1.53 Å / Redundancy: 6.7 % / Mean I/σ(I) obs: 1 / Num. unique obs: 5829 / CC1/2: 0.503 / % possible all: 99.5 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6vn8 Resolution: 1.5→58.46 Å / SU ML: 0.1668 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 21.9037 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 26.34 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.5→58.46 Å
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Refine LS restraints |
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LS refinement shell |
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