+Open data
-Basic information
Entry | Database: PDB / ID: 6gla | ||||||
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Title | Crystal structure of JAK3 in complex with Compound 11 (FM481) | ||||||
Components | Tyrosine-protein kinase JAK3 | ||||||
Keywords | TRANSFERASE / KINASE / JAK3 / COVALENT INHIBITOR / REVERSIBLE COVALENT INHIBITOR / INDUCED POCKET / ARGININE POCKET / STRUCTURAL GENOMICS CONSORTIUM / SGC | ||||||
Function / homology | Function and homology information negative regulation of dendritic cell cytokine production / negative regulation of FasL production / response to interleukin-9 / response to interleukin-2 / response to interleukin-15 / negative regulation of T-helper 17 cell lineage commitment / response to interleukin-4 / negative regulation of T-helper 1 cell differentiation / interleukin-7-mediated signaling pathway / Interleukin-9 signaling ...negative regulation of dendritic cell cytokine production / negative regulation of FasL production / response to interleukin-9 / response to interleukin-2 / response to interleukin-15 / negative regulation of T-helper 17 cell lineage commitment / response to interleukin-4 / negative regulation of T-helper 1 cell differentiation / interleukin-7-mediated signaling pathway / Interleukin-9 signaling / Interleukin-21 signaling / interleukin-9-mediated signaling pathway / negative regulation of T cell activation / interleukin-4-mediated signaling pathway / regulation of T cell apoptotic process / interleukin-2-mediated signaling pathway / negative regulation of interleukin-12 production / tyrosine phosphorylation of STAT protein / interleukin-15-mediated signaling pathway / negative regulation of thymocyte apoptotic process / Interleukin-15 signaling / Interleukin-2 signaling / regulation of receptor signaling pathway via JAK-STAT / growth hormone receptor binding / extrinsic component of plasma membrane / Signaling by ALK / Interleukin-20 family signaling / negative regulation of interleukin-10 production / enzyme-linked receptor protein signaling pathway / T cell homeostasis / extrinsic component of cytoplasmic side of plasma membrane / cell surface receptor signaling pathway via JAK-STAT / growth hormone receptor signaling pathway via JAK-STAT / Interleukin receptor SHC signaling / Interleukin-7 signaling / B cell differentiation / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / cytokine-mediated signaling pathway / peptidyl-tyrosine phosphorylation / cytoplasmic side of plasma membrane / RAF/MAP kinase cascade / protein tyrosine kinase activity / Interleukin-4 and Interleukin-13 signaling / protein phosphatase binding / regulation of apoptotic process / adaptive immune response / Potential therapeutics for SARS / cell differentiation / cytoskeleton / intracellular signal transduction / endosome / protein phosphorylation / innate immune response / ATP binding / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.92 Å | ||||||
Authors | Chaikuad, A. / Forster, M. / von Delft, F. / Edwards, A.M. / Arrowsmith, C.H. / Bountra, C. / Laufer, S.A. / Knapp, S. / Structural Genomics Consortium (SGC) | ||||||
Citation | Journal: J. Med. Chem. / Year: 2018 Title: Development, Optimization, and Structure-Activity Relationships of Covalent-Reversible JAK3 Inhibitors Based on a Tricyclic Imidazo[5,4- d]pyrrolo[2,3- b]pyridine Scaffold. Authors: Forster, M. / Chaikuad, A. / Dimitrov, T. / Doring, E. / Holstein, J. / Berger, B.T. / Gehringer, M. / Ghoreschi, K. / Muller, S. / Knapp, S. / Laufer, S.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6gla.cif.gz | 242.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6gla.ent.gz | 194.6 KB | Display | PDB format |
PDBx/mmJSON format | 6gla.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6gla_validation.pdf.gz | 906.8 KB | Display | wwPDB validaton report |
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Full document | 6gla_full_validation.pdf.gz | 909.8 KB | Display | |
Data in XML | 6gla_validation.xml.gz | 25.2 KB | Display | |
Data in CIF | 6gla_validation.cif.gz | 35.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gl/6gla ftp://data.pdbj.org/pub/pdb/validation_reports/gl/6gla | HTTPS FTP |
-Related structure data
Related structure data | 6gl9C 6glbC 5lwmS 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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2 |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: _ / Ens-ID: 1 / Beg auth comp-ID: ASP / Beg label comp-ID: ASP / End auth comp-ID: ARG / End label comp-ID: ARG / Refine code: _ / Auth seq-ID: 813 - 1103 / Label seq-ID: 4 - 294
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-Components
#1: Protein | Mass: 33417.281 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: JAK3 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P52333, non-specific protein-tyrosine kinase #2: Chemical | #3: Chemical | #4: Chemical | ChemComp-EDO / #5: Water | ChemComp-HOH / | |
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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: 1.93 Å3/Da / Density % sol: 36.35 % |
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Crystal grow | Temperature: 277.15 K / Method: vapor diffusion, sitting drop Details: 24-30% PEG 3350, 0.1 M MES, pH 5.5-6.0 and 0.1-0.2 M MgCl2 PH range: 5.5-6.0 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97625 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: May 16, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97625 Å / Relative weight: 1 |
Reflection | Resolution: 1.92→52.35 Å / Num. obs: 39077 / % possible obs: 99.9 % / Redundancy: 4.1 % / Rmerge(I) obs: 0.146 / Net I/σ(I): 4.9 |
Reflection shell | Resolution: 1.92→2.02 Å / Redundancy: 4 % / Rmerge(I) obs: 0.528 / Mean I/σ(I) obs: 2 / Num. unique obs: 5631 / % possible all: 99.5 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5lwm Resolution: 1.92→52.35 Å / Cor.coef. Fo:Fc: 0.95 / Cor.coef. Fo:Fc free: 0.928 / SU B: 11.952 / SU ML: 0.167 / Cross valid method: THROUGHOUT / ESU R: 0.235 / ESU R Free: 0.195 / 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 26.804 Å2
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Refinement step | Cycle: 1 / Resolution: 1.92→52.35 Å
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Refine LS restraints |
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