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Yorodumi- PDB-7teu: Crystal structure of JAK2 JH1 with type II inhibitor YLIU-04-105-1 -
+Open data
-Basic information
Entry | Database: PDB / ID: 7teu | ||||||
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Title | Crystal structure of JAK2 JH1 with type II inhibitor YLIU-04-105-1 | ||||||
Components | Tyrosine-protein kinase JAK2 | ||||||
Keywords | TRANSFERASE/INHIBITOR / JAK2 / TYROSINE KINASE / INHIBITOR / CYTOKINE SIGNALING / TRANSFERASE / TRANSFERASE-INHIBITOR complex | ||||||
Function / homology | Function and homology information interleukin-35-mediated signaling pathway / intracellular mineralocorticoid receptor 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 / Signaling by Erythropoietin ...interleukin-35-mediated signaling pathway / intracellular mineralocorticoid receptor 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 / Signaling by Erythropoietin / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / interleukin-12 receptor binding / post-embryonic hemopoiesis / collagen-activated signaling pathway / Erythropoietin activates STAT5 / Erythropoietin activates Phospholipase C gamma (PLCG) / interleukin-5-mediated signaling pathway / response to interleukin-12 / positive regulation of leukocyte proliferation / interleukin-12 receptor complex / activation of Janus kinase activity / interleukin-23 receptor complex / positive regulation of platelet aggregation / tyrosine phosphorylation of STAT protein / Interleukin-23 signaling / positive regulation of MHC class II biosynthetic process / positive regulation of T-helper 17 type immune response / positive regulation of platelet activation / type 1 angiotensin receptor binding / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / interleukin-3-mediated signaling pathway / regulation of nitric oxide biosynthetic process / acetylcholine receptor binding / cellular response to interleukin-3 / Signaling by Leptin / Interleukin-12 signaling / positive regulation of signaling receptor activity / Interleukin-35 Signalling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / positive regulation of cell-substrate adhesion / response to hydroperoxide / regulation of receptor signaling pathway via JAK-STAT / growth hormone receptor binding / negative regulation of cardiac muscle cell apoptotic process / positive regulation of natural killer cell proliferation / positive regulation of epithelial cell apoptotic process / axon regeneration / growth hormone receptor signaling pathway / peptide hormone receptor binding / 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 / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / negative regulation of cell-cell adhesion / Interleukin-6 signaling / enzyme-linked receptor protein signaling pathway / Prolactin receptor signaling / positive regulation of interleukin-17 production / MAPK3 (ERK1) activation / negative regulation of DNA binding / response to amine / positive regulation of nitric-oxide synthase biosynthetic process / 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 / growth hormone receptor signaling pathway via JAK-STAT / response to tumor necrosis factor / Interleukin receptor SHC signaling / phosphatidylinositol 3-kinase binding / type II interferon-mediated signaling pathway / Regulation of IFNG signaling / 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 / post-translational protein modification / cellular response to dexamethasone stimulus / erythrocyte differentiation / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / positive regulation of interleukin-1 beta production / positive regulation of apoptotic signaling pathway / caveola / endosome lumen / positive regulation of cell differentiation Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.45 Å | ||||||
Authors | Hubbard, S.R. | ||||||
Funding support | United States, 1items
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Citation | Journal: Cell Chem Biol / Year: 2023 Title: New scaffolds for type II JAK2 inhibitors overcome the acquired G993A resistance mutation. Authors: Arwood, M.L. / Liu, Y. / Harkins, S.K. / Weinstock, D.M. / Yang, L. / Stevenson, K.E. / Plana, O.D. / Dong, J. / Cirka, H. / Jones, K.L. / Virtanen, A.T. / Gupta, D.G. / Ceas, A. / Lawney, B. ...Authors: Arwood, M.L. / Liu, Y. / Harkins, S.K. / Weinstock, D.M. / Yang, L. / Stevenson, K.E. / Plana, O.D. / Dong, J. / Cirka, H. / Jones, K.L. / Virtanen, A.T. / Gupta, D.G. / Ceas, A. / Lawney, B. / Yoda, A. / Leahy, C. / Hao, M. / He, Z. / Choi, H.G. / Wang, Y. / Silvennoinen, O. / Hubbard, S.R. / Zhang, T. / Gray, N.S. / Li, L.S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7teu.cif.gz | 94.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7teu.ent.gz | 55.2 KB | Display | PDB format |
PDBx/mmJSON format | 7teu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/te/7teu ftp://data.pdbj.org/pub/pdb/validation_reports/te/7teu | HTTPS FTP |
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-Related structure data
Related structure data | 3ugcS S: Starting model for refinement |
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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 on special symmetry positions |
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-Components
#1: Protein | Mass: 37090.348 Da / Num. of mol.: 1 / Mutation: Y1007F, Y1008F Source method: isolated from a genetically manipulated source Details: TYROSINE KINASE DOMAIN (JH1) / Source: (gene. exp.) Homo sapiens (human) / Gene: JAK2 / Plasmid: pET15b / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: O60674, non-specific protein-tyrosine kinase |
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#2: Chemical | ChemComp-I6C / |
#3: Chemical | ChemComp-GOL / |
#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: 2.55 Å3/Da / Density % sol: 51.84 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 4 Details: 200 mM potassium phosphate monobasic, 21% (w/v) PEG 3350 |
-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: 0.979 Å |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Mar 19, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.979 Å / Relative weight: 1 |
Reflection | Resolution: 1.45→28.7 Å / Num. obs: 65627 / % possible obs: 99 % / Redundancy: 4.8 % / Biso Wilson estimate: 14.45 Å2 / CC1/2: 1 / CC star: 1 / Rmerge(I) obs: 0.05 / Rpim(I) all: 0.025 / Rrim(I) all: 0.056 / Net I/σ(I): 19.6 |
Reflection shell | Resolution: 1.45→1.5 Å / Redundancy: 3.7 % / Rmerge(I) obs: 0.33 / Mean I/σ(I) obs: 5.61 / Num. unique obs: 6373 / CC1/2: 0.9 / CC star: 0.97 / Rpim(I) all: 0.19 / Rrim(I) all: 0.38 / % possible all: 97 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3UGC Resolution: 1.45→28.68 Å / SU ML: 0.1192 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 20.654 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: 20.82 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.45→28.68 Å
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Refine LS restraints |
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LS refinement shell |
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