+Open data
-Basic information
Entry | Database: PDB / ID: 4jia | ||||||
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Title | JAK2 kinase (JH1 domain) in complex with compound 9 | ||||||
Components | Tyrosine-protein kinase JAK2 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / protein kinase / phosphotransfer / 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 / : / 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 / : / 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 / granulocyte macrophage colony-stimulating factor receptor complex / granulocyte-macrophage colony-stimulating factor signaling pathway / Signaling by Erythropoietin / collagen-activated signaling pathway / interleukin-23-mediated signaling pathway / interleukin-12 receptor binding / Erythropoietin activates STAT5 / response to interleukin-12 / interleukin-5-mediated signaling pathway / 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 / interleukin-12-mediated signaling pathway / acetylcholine receptor binding / positive regulation of platelet activation / 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 / Interleukin-20 family signaling / IFNG signaling activates MAPKs / 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 / response to amine / negative regulation of DNA binding / positive regulation of interleukin-17 production / extrinsic component of cytoplasmic side of plasma membrane / positive regulation of nitric-oxide synthase biosynthetic process / mesoderm development / MAPK1 (ERK2) activation / 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 / type II interferon-mediated signaling pathway / growth hormone receptor signaling pathway via JAK-STAT / Interleukin receptor SHC signaling / phosphatidylinositol 3-kinase binding / Regulation of IFNG signaling / positive regulation of tyrosine phosphorylation of STAT protein / Erythropoietin activates RAS / Signaling by CSF3 (G-CSF) / positive regulation of T cell proliferation / Growth hormone receptor signaling / extrinsic apoptotic signaling pathway / positive regulation of vascular associated smooth muscle cell proliferation / tumor necrosis factor-mediated signaling pathway / actin filament polymerization / post-translational protein modification / SH2 domain binding / cellular response to dexamethasone stimulus / 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 / Resolution: 1.85 Å | ||||||
Authors | Eigenbrot, C. / Ultsch, M. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2013 Title: 2-Amino-[1,2,4]triazolo[1,5-a]pyridines as JAK2 inhibitors. Authors: Siu, M. / Pastor, R. / Liu, W. / Barrett, K. / Berry, M. / Blair, W.S. / Chang, C. / Chen, J.Z. / Eigenbrot, C. / Ghilardi, N. / Gibbons, P. / He, H. / Hurley, C.A. / Kenny, J.R. / Cyrus ...Authors: Siu, M. / Pastor, R. / Liu, W. / Barrett, K. / Berry, M. / Blair, W.S. / Chang, C. / Chen, J.Z. / Eigenbrot, C. / Ghilardi, N. / Gibbons, P. / He, H. / Hurley, C.A. / Kenny, J.R. / Cyrus Khojasteh, S. / Le, H. / Lee, L. / Lyssikatos, J.P. / Magnuson, S. / Pulk, R. / Tsui, V. / Ultsch, M. / Xiao, Y. / Zhu, B.Y. / Sampath, D. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4jia.cif.gz | 82.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4jia.ent.gz | 60.1 KB | Display | PDB format |
PDBx/mmJSON format | 4jia.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4jia_validation.pdf.gz | 716.1 KB | Display | wwPDB validaton report |
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Full document | 4jia_full_validation.pdf.gz | 719.7 KB | Display | |
Data in XML | 4jia_validation.xml.gz | 14.9 KB | Display | |
Data in CIF | 4jia_validation.cif.gz | 21 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ji/4jia ftp://data.pdbj.org/pub/pdb/validation_reports/ji/4jia | HTTPS FTP |
-Related structure data
Related structure data | 4ji9C 2b7aS 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
#1: Protein | Mass: 35342.125 Da / Num. of mol.: 1 / Fragment: JH1 domain, UNP residues 833-1132 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-1K3 / |
#3: Chemical | ChemComp-GOL / |
#4: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION |
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-Sample preparation
Crystal | Density Matthews: 2.66 Å3/Da / Density % sol: 53.81 % |
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Crystal grow | Temperature: 300 K / Method: vapor diffusion, hanging drop / pH: 6 Details: ammonium acetate, PEG 8000, pH 6, VAPOR DIFFUSION, HANGING DROP, temperature 300K |
-Data collection
Diffraction | Mean temperature: 110 K |
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Feb 6, 2008 |
Radiation | Monochromator: Si 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.85→50 Å / Num. all: 31803 / Num. obs: 31686 / % possible obs: 99.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 3.4 % / Biso Wilson estimate: 19 Å2 / Rsym value: 0.114 / Net I/σ(I): 15 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 2B7A Resolution: 1.85→50 Å / Cor.coef. Fo:Fc: 0.956 / Cor.coef. Fo:Fc free: 0.945 / SU B: 2.435 / SU ML: 0.074 / Isotropic thermal model: individual atoms / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.122 / ESU R Free: 0.115 / 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: 1.4 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 20.311 Å2
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Refinement step | Cycle: LAST / Resolution: 1.85→50 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.85→1.95 Å / Total num. of bins used: 10
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