+Open data
-Basic information
Entry | Database: PDB / ID: 7t0p | ||||||
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Title | JAK2 JH2 IN COMPLEX WITH JAK315 | ||||||
Components | Tyrosine-protein kinase JAK2 | ||||||
Keywords | TRANSFERASE/INHIBITOR / PSEUDOKINASE DOMAIN / INHIBITOR / COMPLEX / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX / SIGNALING PROTEIN / 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 / 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 / MOLECULAR REPLACEMENT / Resolution: 2.04 Å | ||||||
Authors | Ippolito, J.A. / Liosi, M.-E. / Krimmer, S.G. / Schlessinger, J. / Jorgensen, W.L. | ||||||
Funding support | United States, 1items
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Citation | Journal: J.Med.Chem. / Year: 2022 Title: Insights on JAK2 Modulation by Potent, Selective, and Cell-Permeable Pseudokinase-Domain Ligands. Authors: Liosi, M.E. / Ippolito, J.A. / Henry, S.P. / Krimmer, S.G. / Newton, A.S. / Cutrona, K.J. / Olivarez, R.A. / Mohanty, J. / Schlessinger, J. / Jorgensen, W.L. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7t0p.cif.gz | 131.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7t0p.ent.gz | 98 KB | Display | PDB format |
PDBx/mmJSON format | 7t0p.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7t0p_validation.pdf.gz | 946.5 KB | Display | wwPDB validaton report |
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Full document | 7t0p_full_validation.pdf.gz | 953.9 KB | Display | |
Data in XML | 7t0p_validation.xml.gz | 25.3 KB | Display | |
Data in CIF | 7t0p_validation.cif.gz | 35.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t0/7t0p ftp://data.pdbj.org/pub/pdb/validation_reports/t0/7t0p | HTTPS FTP |
-Related structure data
Related structure data | 7szwC 6occS 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
#1: Protein | Mass: 33120.961 Da / Num. of mol.: 2 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 #2: Chemical | #3: Chemical | #4: 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: 2.29 Å3/Da / Density % sol: 46.18 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop Details: 0.1M TRIS, PH 8.0 0.2M SODIUM ACETATE, 0.001 M TCEP, 12-24% PEG 4,000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.54 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: RIGAKU SATURN 944+ / Detector: CCD / Date: May 13, 2021 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.54 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.04→19.19 Å / Num. obs: 34789 / % possible obs: 93 % / Redundancy: 3.836 % / Biso Wilson estimate: 23.991 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.08 / Rrim(I) all: 0.094 / Χ2: 0.886 / Net I/σ(I): 13.38 / Num. measured all: 133449 / Scaling rejects: 833 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6occ Resolution: 2.04→19.19 Å / SU ML: 0.24 / Cross valid method: THROUGHOUT / σ(F): 1.99 / Phase error: 27.8 / Stereochemistry target values: ML
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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 max: 71.09 Å2 / Biso mean: 21.2521 Å2 / Biso min: 7.39 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.04→19.19 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 13
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