+Open data
-Basic information
Entry | Database: PDB / ID: 5ut0 | |||||||||
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Title | JAK2 JH2 in complex with AT9283 | |||||||||
Components | Tyrosine-protein kinase JAK2 | |||||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / Pseudokinase Domain / TRANSFERASE-TRANSFERASE INHIBITOR complex | |||||||||
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 / interleukin-12 receptor binding / Signaling by Erythropoietin / collagen-activated signaling pathway / 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 / interleukin-23 receptor complex / tyrosine phosphorylation of STAT protein / Interleukin-23 signaling / positive regulation of MHC class II biosynthetic process / positive regulation of platelet aggregation / positive regulation of T-helper 17 type immune response / type 1 angiotensin receptor binding / positive regulation of platelet activation / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / acetylcholine receptor binding / 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-35 Signalling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / positive regulation of epithelial cell apoptotic process / positive regulation of natural killer cell proliferation / response to hydroperoxide / 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 / IFNG signaling activates MAPKs / extrinsic component of plasma membrane / 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 / positive regulation of interleukin-17 production / response to amine / negative regulation of DNA binding / positive regulation of nitric-oxide synthase biosynthetic process / MAPK1 (ERK2) activation / cell surface receptor signaling pathway via JAK-STAT / mesoderm development / 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 / positive regulation of T cell proliferation / extrinsic apoptotic signaling pathway / 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 / MOLECULAR REPLACEMENT / Resolution: 2.102 Å | |||||||||
Authors | Puleo, D.E. / Schlessinger, J. | |||||||||
Funding support | United States, 2items
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Citation | Journal: ACS Med Chem Lett / Year: 2017 Title: Identification and Characterization of JAK2 Pseudokinase Domain Small Molecule Binders. Authors: Puleo, D.E. / Kucera, K. / Hammaren, H.M. / Ungureanu, D. / Newton, A.S. / Silvennoinen, O. / Jorgensen, W.L. / Schlessinger, J. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5ut0.cif.gz | 129.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5ut0.ent.gz | 96.7 KB | Display | PDB format |
PDBx/mmJSON format | 5ut0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5ut0_validation.pdf.gz | 736.1 KB | Display | wwPDB validaton report |
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Full document | 5ut0_full_validation.pdf.gz | 737.3 KB | Display | |
Data in XML | 5ut0_validation.xml.gz | 14.9 KB | Display | |
Data in CIF | 5ut0_validation.cif.gz | 21.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ut/5ut0 ftp://data.pdbj.org/pub/pdb/validation_reports/ut/5ut0 | HTTPS FTP |
-Related structure data
Related structure data | 5usyC 5uszC 5ut1C 5ut2C 5ut3C 4fvpS C: citing same article (ref.) S: Starting model for refinement |
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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
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 33120.961 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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-Non-polymers , 5 types, 251 molecules
#2: Chemical | #3: Chemical | ChemComp-35R / | #4: Chemical | ChemComp-ACT / | #5: Chemical | ChemComp-DMS / | #6: Water | ChemComp-HOH / | |
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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: 2.18 Å3/Da / Density % sol: 43.67 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 8 Details: 0.1M Tris pH 8.0 0.2M Sodium acetate 12-20% PEG 4,000 PH range: 7.5-8.5 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.54 Å |
Detector | Type: DECTRIS PILATUS 200K / Detector: PIXEL / Date: Mar 14, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54 Å / Relative weight: 1 |
Reflection | Resolution: 2.1→41.486 Å / Num. obs: 16717 / % possible obs: 99.9 % / Redundancy: 3.6 % / Rsym value: 0.11 / Net I/σ(I): 8.9 |
Reflection shell | Resolution: 2.1→2.18 Å / Redundancy: 2.4 % / Mean I/σ(I) obs: 1.9 / Rsym value: 0.323 / % possible all: 99.7 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4FVP Resolution: 2.102→41.486 Å / SU ML: 0.2 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 21.37
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.102→41.486 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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