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- PDB-5wev: Identification of an imidazopyridine scaffold to generate potent ... -
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Basic information
Entry | Database: PDB / ID: 5wev | ||||||
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Title | Identification of an imidazopyridine scaffold to generate potent and selective TYK2 inhibitors that demonstrate activity in an in vivo psoriasis model | ||||||
![]() | Tyrosine-protein kinase JAK2 | ||||||
![]() | Transferase/Transferase Inhibitor / Jak2 / Kinase / Inhibitor / Transferase-Transferase Inhibitor complex | ||||||
Function / homology | ![]() 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 | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Ultsch, M.H. / Magnuson, S. | ||||||
![]() | ![]() Title: Identification of an imidazopyridine scaffold to generate potent and selective TYK2 inhibitors that demonstrate activity in an in vivo psoriasis model. Authors: Liang, J. / Van Abbema, A. / Balazs, M. / Barrett, K. / Berezhkovsky, L. / Blair, W.S. / Chang, C. / Delarosa, D. / DeVoss, J. / Driscoll, J. / Eigenbrot, C. / Goodacre, S. / Ghilardi, N. / ...Authors: Liang, J. / Van Abbema, A. / Balazs, M. / Barrett, K. / Berezhkovsky, L. / Blair, W.S. / Chang, C. / Delarosa, D. / DeVoss, J. / Driscoll, J. / Eigenbrot, C. / Goodacre, S. / Ghilardi, N. / MacLeod, C. / Johnson, A. / Bir Kohli, P. / Lai, Y. / Lin, Z. / Mantik, P. / Menghrajani, K. / Nguyen, H. / Peng, I. / Sambrone, A. / Shia, S. / Smith, J. / Sohn, S. / Tsui, V. / Ultsch, M. / Williams, K. / Wu, L.C. / Yang, W. / Zhang, B. / Magnuson, S. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 82.2 KB | Display | ![]() |
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PDB format | ![]() | 58.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 781.7 KB | Display | ![]() |
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Full document | ![]() | 783.9 KB | Display | |
Data in XML | ![]() | 14.5 KB | Display | |
Data in CIF | ![]() | 20.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5walC ![]() 2b7aS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 37375.340 Da / Num. of mol.: 1 / Fragment: UNP residues 833-1132 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: O60674, non-specific protein-tyrosine kinase |
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#2: Chemical | ChemComp-9ZS / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.5 Å3/Da / Density % sol: 50.89 % / Description: Rods |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 6 Details: 25-30% w/v PEG 8000 0.2M Ammonium Acetate 0.1M Na Citrate pH 6.0 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: ADSC QUANTUM 315r / Detector: CCD / Date: Oct 10, 2009 |
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: 1.854→50.01 Å / Num. obs: 31177 / % possible obs: 99.8 % / Observed criterion σ(I): 2 / Redundancy: 3.6 % / Rsym value: 0.067 / Net I/σ(I): 19.1 |
Reflection shell | Resolution: 1.854→1.92 Å / Redundancy: 3.6 % / Num. unique obs: 10692 / Rsym value: 0.424 / % possible all: 99.7 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 2B7A Resolution: 1.854→40 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.958 / SU B: 2.504 / SU ML: 0.075 / Cross valid method: THROUGHOUT / ESU R: 0.117 / ESU R Free: 0.11 / Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 27.966 Å2
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Refinement step | Cycle: 1 / Resolution: 1.854→40 Å
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Refine LS restraints |
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