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Yorodumi- PDB-6wtq: Human JAK2 JH1 domain in complex with PROTAC-intermediate linker ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6wtq | ||||||
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Title | Human JAK2 JH1 domain in complex with PROTAC-intermediate linker handle 4 | ||||||
Components | Tyrosine-protein kinase JAK2 | ||||||
Keywords | TRANSFERASE / 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 / molecular replacement / Resolution: 1.79968475557 Å | ||||||
Authors | Yu, S. / Nithianantham, S. / Fischer, M. | ||||||
Citation | Journal: Blood / Year: 2021 Title: Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia. Authors: Chang, Y. / Min, J. / Jarusiewicz, J.A. / Actis, M. / Yu-Chen Bradford, S. / Mayasundari, A. / Yang, L. / Chepyala, D. / Alcock, L.J. / Roberts, K.G. / Nithianantham, S. / Maxwell, D. / ...Authors: Chang, Y. / Min, J. / Jarusiewicz, J.A. / Actis, M. / Yu-Chen Bradford, S. / Mayasundari, A. / Yang, L. / Chepyala, D. / Alcock, L.J. / Roberts, K.G. / Nithianantham, S. / Maxwell, D. / Rowland, L. / Larsen, R. / Seth, A. / Goto, H. / Imamura, T. / Akahane, K. / Hansen, B.S. / Pruett-Miller, S.M. / Paietta, E.M. / Litzow, M.R. / Qu, C. / Yang, J.J. / Fischer, M. / Rankovic, Z. / Mullighan, C.G. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6wtq.cif.gz | 153.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6wtq.ent.gz | 98.6 KB | Display | PDB format |
PDBx/mmJSON format | 6wtq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6wtq_validation.pdf.gz | 698.4 KB | Display | wwPDB validaton report |
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Full document | 6wtq_full_validation.pdf.gz | 700.7 KB | Display | |
Data in XML | 6wtq_validation.xml.gz | 12.7 KB | Display | |
Data in CIF | 6wtq_validation.cif.gz | 16.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wt/6wtq ftp://data.pdbj.org/pub/pdb/validation_reports/wt/6wtq | HTTPS FTP |
-Related structure data
Related structure data | 6wtnC 6wtoC 6wtpC 5usyS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 36412.297 Da / Num. of mol.: 1 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-U8J / |
#3: Chemical | ChemComp-TRS / |
#4: Chemical | ChemComp-EDO / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | Y |
Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.11 Å3/Da / Density % sol: 41.79 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 5 Details: 0.1 M SODIUM CITRATE PH 6.5, 27% PEG 8000 AND 0.2 M AMMONIUM ACETATE. REMARK 280 6.5, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 291K |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å | ||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 8, 2019 | ||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | ||||||||||||||||||||||||
Reflection | Resolution: 1.799→36.04 Å / Num. obs: 29041 / % possible obs: 100 % / Redundancy: 6.9 % / CC1/2: 0.998 / Rmerge(I) obs: 0.077 / Rpim(I) all: 0.031 / Rrim(I) all: 0.083 / Net I/σ(I): 11.7 | ||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5USY Resolution: 1.79968475557→36.0364456181 Å / SU ML: 0.207470936773 / Cross valid method: THROUGHOUT / σ(F): 1.33541549176 / Phase error: 22.2719531125 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 1.2 Å / VDW probe radii: 1.4 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 43.3181747434 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.79968475557→36.0364456181 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 32.902625705 Å / Origin y: -8.81737606413 Å / Origin z: 5.93155049998 Å
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Refinement TLS group | Selection details: all |