+Open data
-Basic information
Entry | Database: PDB / ID: 8g8o | ||||||
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Title | The crystal structure of JAK2 in complex with Compound 31 | ||||||
Components | Tyrosine-protein kinase JAK2 | ||||||
Keywords | TRANSFERASE/Inhibitor / inhibitor / JAK2 / kinase / 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 / 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 MHC class II biosynthetic process / positive regulation of platelet aggregation / Interleukin-23 signaling / type 1 angiotensin receptor binding / positive regulation of T-helper 17 type immune response / positive regulation of platelet activation / acetylcholine receptor binding / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / 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-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / positive regulation of epithelial cell apoptotic process / response to hydroperoxide / 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 / 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 / extrinsic component of plasma membrane / IFNG signaling activates MAPKs / 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 / response to amine / positive regulation of interleukin-17 production / negative regulation of DNA binding / positive regulation of nitric-oxide synthase biosynthetic process / MAPK1 (ERK2) activation / mesoderm development / cell surface receptor signaling pathway via JAK-STAT / 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 / 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 / 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 / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å | ||||||
Authors | Miller, S.T. / Ellis, D.A. | ||||||
Funding support | 1items
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Citation | Journal: J.Med.Chem. / Year: 2023 Title: Eyes on Topical Ocular Disposition: The Considered Design of a Lead Janus Kinase (JAK) Inhibitor That Utilizes a Unique Azetidin-3-Amino Bridging Scaffold to Attenuate Off-Target Kinase ...Title: Eyes on Topical Ocular Disposition: The Considered Design of a Lead Janus Kinase (JAK) Inhibitor That Utilizes a Unique Azetidin-3-Amino Bridging Scaffold to Attenuate Off-Target Kinase Activity, While Driving Potency and Aqueous Solubility. Authors: Gordhan, H.M. / Miller, S.T. / Clancy, D.C. / Ina, M. / McDougal, A.V. / Cutno, D.K. / Brown, R.V. / Lichorowic, C.L. / Sturdivant, J.M. / Vick, K.A. / Williams, S.S. / deLong, M.A. / White, ...Authors: Gordhan, H.M. / Miller, S.T. / Clancy, D.C. / Ina, M. / McDougal, A.V. / Cutno, D.K. / Brown, R.V. / Lichorowic, C.L. / Sturdivant, J.M. / Vick, K.A. / Williams, S.S. / deLong, M.A. / White, J.C. / Kopczynski, C.C. / Ellis, D.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8g8o.cif.gz | 135.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8g8o.ent.gz | 102.3 KB | Display | PDB format |
PDBx/mmJSON format | 8g8o.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8g8o_validation.pdf.gz | 1006 KB | Display | wwPDB validaton report |
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Full document | 8g8o_full_validation.pdf.gz | 1010.1 KB | Display | |
Data in XML | 8g8o_validation.xml.gz | 23 KB | Display | |
Data in CIF | 8g8o_validation.cif.gz | 31.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/g8/8g8o ftp://data.pdbj.org/pub/pdb/validation_reports/g8/8g8o | HTTPS FTP |
-Related structure data
Related structure data | 8g6zC 8g8xC 3iokS 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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Unit cell |
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-Components
#1: Protein | Mass: 37458.535 Da / Num. of mol.: 2 / Mutation: M1073S, F1076T 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 | ChemComp-DMS / | #4: Chemical | ChemComp-EDO / | #5: 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: 2.14 Å3/Da / Density % sol: 42.54 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / Details: PEG 3350, ammonium acetate, HEPES |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9763 Å |
Detector | Type: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Jun 27, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9763 Å / Relative weight: 1 |
Reflection | Resolution: 2.2→47.18 Å / Num. obs: 31923 / % possible obs: 99.9 % / Redundancy: 6.5 % / Rmerge(I) obs: 0.175 / Rpim(I) all: 0.075 / Net I/σ(I): 8.2 |
Reflection shell | Resolution: 2.2→2.27 Å / Rmerge(I) obs: 1.319 / Mean I/σ(I) obs: 1.5 / Num. unique obs: 2810 / Rpim(I) all: 0.534 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3IOK Resolution: 2.2→47.18 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.921 / SU B: 4.22 / SU ML: 0.116 / Cross valid method: THROUGHOUT / ESU R: 0.058 / ESU R Free: 0.044 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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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 mean: 38.111 Å2
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Refinement step | Cycle: 1 / Resolution: 2.2→47.18 Å
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