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Yorodumi- PDB-7uyw: Crystal structure of JAK2 kinase domain in complex with compound 30 -
+Open data
-Basic information
Entry | Database: PDB / ID: 7uyw | ||||||
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Title | Crystal structure of JAK2 kinase domain in complex with compound 30 | ||||||
Components | Tyrosine-protein kinase JAK2 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / non-receptor tyrosine-protein kinase JAK2 / 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 / activation of Janus kinase activity / interleukin-12 receptor complex / 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 platelet activation / positive regulation of T-helper 17 type immune response / 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 / 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 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 epithelial cell apoptotic process / axon regeneration / peptide hormone receptor binding / growth hormone receptor signaling pathway / intrinsic apoptotic signaling pathway in response to oxidative stress / IFNG signaling activates MAPKs / extrinsic component of plasma membrane / Interleukin-20 family signaling / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / Interleukin-6 signaling / enzyme-linked receptor protein signaling pathway / interleukin-6-mediated signaling pathway / negative regulation of cell-cell adhesion / Prolactin receptor signaling / positive regulation of interleukin-17 production / negative regulation of DNA binding / MAPK3 (ERK1) activation / response to amine / positive regulation of nitric-oxide synthase biosynthetic process / MAPK1 (ERK2) activation / positive regulation of natural killer cell proliferation / 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 / positive regulation of apoptotic signaling pathway / extrinsic apoptotic signaling pathway / Signaling by CSF3 (G-CSF) / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of vascular associated smooth muscle cell proliferation / positive regulation of T cell proliferation / tumor necrosis factor-mediated signaling pathway / actin filament polymerization / extrinsic component of cytoplasmic side of plasma membrane / 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 / caveola / 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: 2.51 Å | ||||||
Authors | Toms, A.V. / Leit, S. / Greenwood, J.R. / Mondal, S. / Carriero, S. / Dahlgren, M. / Harriman, G.C. / Kennedy-Smith, J.J. / Kapeller, R. / Lawson, J.P. ...Toms, A.V. / Leit, S. / Greenwood, J.R. / Mondal, S. / Carriero, S. / Dahlgren, M. / Harriman, G.C. / Kennedy-Smith, J.J. / Kapeller, R. / Lawson, J.P. / Romero, D.L. / Shelley, M. / Wester, R.T. / Westlin, W. / Mc Elwee, J.J. / Miao, W. / Edmondson, S.D. / Massee, C.E. | ||||||
Funding support | 1items
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Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2022 Title: Potent and selective TYK2-JH1 inhibitors highly efficacious in rodent model of psoriasis. Authors: Leit, S. / Greenwood, J.R. / Mondal, S. / Carriero, S. / Dahlgren, M. / Harriman, G.C. / Kennedy-Smith, J.J. / Kapeller, R. / Lawson, J.P. / Romero, D.L. / Toms, A.V. / Shelley, M. / Wester, ...Authors: Leit, S. / Greenwood, J.R. / Mondal, S. / Carriero, S. / Dahlgren, M. / Harriman, G.C. / Kennedy-Smith, J.J. / Kapeller, R. / Lawson, J.P. / Romero, D.L. / Toms, A.V. / Shelley, M. / Wester, R.T. / Westlin, W. / McElwee, J.J. / Miao, W. / Edmondson, S.D. / Masse, C.E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7uyw.cif.gz | 71.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7uyw.ent.gz | 53.9 KB | Display | PDB format |
PDBx/mmJSON format | 7uyw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uy/7uyw ftp://data.pdbj.org/pub/pdb/validation_reports/uy/7uyw | HTTPS FTP |
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-Related structure data
Related structure data | 7uyrC 7uysC 7uytC 7uyuC 7uyvC 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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Unit cell |
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-Components
#1: Protein | Mass: 34366.152 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN 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-OV0 / |
#3: 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: 2.52 Å3/Da / Density % sol: 51.21 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion Details: Crystals of human JAK2 in complex with the ligand were prepared according to established protocols |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.999988913536 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 15, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.999988913536 Å / Relative weight: 1 |
Reflection | Resolution: 2.51→69.37 Å / Num. obs: 12116 / % possible obs: 99.6 % / Redundancy: 5.8 % / Rmerge(I) obs: 0.084 / Net I/σ(I): 17.88 |
Reflection shell | Resolution: 2.51→2.72 Å / Redundancy: 5.5 % / Rmerge(I) obs: 0.437 / Mean I/σ(I) obs: 5.12 / Num. unique obs: 2969 / Rrim(I) all: 0.483 / % possible all: 99.2 |
-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: NONE Resolution: 2.51→69.37 Å / Cor.coef. Fo:Fc: 0.941 / Cor.coef. Fo:Fc free: 0.907 / SU B: 10.641 / SU ML: 0.232 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.877 / ESU R Free: 0.323 / Stereochemistry target values: MAXIMUM LIKELIHOOD Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 130.5 Å2 / Biso mean: 42.702 Å2 / Biso min: 4.82 Å2
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Refinement step | Cycle: final / Resolution: 2.51→69.37 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.51→2.575 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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