+Open data
-Basic information
Entry | Database: PDB / ID: 6w8l | ||||||
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Title | Crystal structure of JAK1 kinase with compound 10 | ||||||
Components | Tyrosine-protein kinase JAK1 | ||||||
Keywords | TRANSFERASE/INHIBITOR / kinase / TRANSFERASE / TRANSFERASE-INHIBITOR complex | ||||||
Function / homology | Function and homology information protein localization to cell-cell junction / interleukin-11-mediated signaling pathway / CCR5 chemokine receptor binding / type III interferon-mediated signaling pathway / T-helper 17 cell lineage commitment / positive regulation of homotypic cell-cell adhesion / Interleukin-9 signaling / Interleukin-21 signaling / interleukin-9-mediated signaling pathway / interleukin-10-mediated signaling pathway ...protein localization to cell-cell junction / interleukin-11-mediated signaling pathway / CCR5 chemokine receptor binding / type III interferon-mediated signaling pathway / T-helper 17 cell lineage commitment / positive regulation of homotypic cell-cell adhesion / Interleukin-9 signaling / Interleukin-21 signaling / interleukin-9-mediated signaling pathway / interleukin-10-mediated signaling pathway / interleukin-4-mediated signaling pathway / interleukin-2-mediated signaling pathway / interleukin-15-mediated signaling pathway / Interleukin-15 signaling / Interleukin-12 signaling / Interleukin-27 signaling / IL-6-type cytokine receptor ligand interactions / Interleukin-35 Signalling / Interleukin-2 signaling / growth hormone receptor binding / Other interleukin signaling / IFNG signaling activates MAPKs / Interleukin-20 family signaling / interleukin-6-mediated signaling pathway / type I interferon-mediated signaling pathway / Interleukin-6 signaling / positive regulation of sprouting angiogenesis / MAPK3 (ERK1) activation / Interleukin-10 signaling / extrinsic component of cytoplasmic side of plasma membrane / MAPK1 (ERK2) activation / cell surface receptor signaling pathway via JAK-STAT / Regulation of IFNA/IFNB signaling / growth hormone receptor signaling pathway via JAK-STAT / Interleukin receptor SHC signaling / Regulation of IFNG signaling / type II interferon-mediated signaling pathway / Signaling by CSF3 (G-CSF) / Interleukin-7 signaling / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / Inactivation of CSF3 (G-CSF) signaling / Evasion by RSV of host interferon responses / cytoplasmic side of plasma membrane / cellular response to virus / ISG15 antiviral mechanism / cytokine-mediated signaling pathway / positive regulation of protein localization to nucleus / Interferon gamma signaling / Interferon alpha/beta signaling / RAF/MAP kinase cascade / protein phosphatase binding / protein tyrosine kinase activity / Potential therapeutics for SARS / Interleukin-4 and Interleukin-13 signaling / endosome / cell differentiation / cytoskeleton / intracellular signal transduction / protein phosphorylation / response to antibiotic / focal adhesion / ubiquitin protein ligase binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / ATP binding / nucleus / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.11 Å | ||||||
Authors | Vajdos, F.F. | ||||||
Citation | Journal: Bioorg.Med.Chem. / Year: 2020 Title: Design and optimization of a series of 4-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-2-amines: Dual inhibitors of TYK2 and JAK1. Authors: Fensome, A. / Ambler, C.M. / Arnold, E. / Banker, M.E. / Clark, J.D. / Dowty, M.E. / Efremov, I.V. / Flick, A. / Gerstenberger, B.S. / Gifford, R.S. / Gopalsamy, A. / Hegen, M. / Jussif, J. ...Authors: Fensome, A. / Ambler, C.M. / Arnold, E. / Banker, M.E. / Clark, J.D. / Dowty, M.E. / Efremov, I.V. / Flick, A. / Gerstenberger, B.S. / Gifford, R.S. / Gopalsamy, A. / Hegen, M. / Jussif, J. / Limburg, D.C. / Lin, T.H. / Pierce, B.S. / Sharma, R. / Trujillo, J.I. / Vajdos, F.F. / Vincent, F. / Wan, Z.K. / Xing, L. / Yang, X. / Yang, X. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6w8l.cif.gz | 135.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6w8l.ent.gz | 102.6 KB | Display | PDB format |
PDBx/mmJSON format | 6w8l.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6w8l_validation.pdf.gz | 754.8 KB | Display | wwPDB validaton report |
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Full document | 6w8l_full_validation.pdf.gz | 757 KB | Display | |
Data in XML | 6w8l_validation.xml.gz | 12.4 KB | Display | |
Data in CIF | 6w8l_validation.cif.gz | 16.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w8/6w8l ftp://data.pdbj.org/pub/pdb/validation_reports/w8/6w8l | HTTPS FTP |
-Related structure data
Related structure data | 6vnsC 6vnvC 6vnxC 6vnyC 6dbnS S: Starting model for refinement C: citing same article (ref.) |
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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: 36417.469 Da / Num. of mol.: 1 / Fragment: kinase domain Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: JAK1, JAK1A, JAK1B / Cell line (production host): Sf21 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P23458, non-specific protein-tyrosine kinase |
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#2: Chemical | ChemComp-R4S / |
#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: 2.05 Å3/Da / Density % sol: 40.14 % |
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Crystal grow | Temperature: 298 K / Method: evaporation / pH: 8 / Details: 0.1 M Tris pH 8.5, 6-9% MPD, 24-29% PEG-1500 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | |||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å | |||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 27, 2018 | |||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 | |||||||||||||||||||||||||||
Reflection | Resolution: 2.11→73.38 Å / Num. obs: 17476 / % possible obs: 98.7 % / Redundancy: 6.4 % / Biso Wilson estimate: 42.14 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.111 / Rpim(I) all: 0.049 / Rrim(I) all: 0.121 / Net I/σ(I): 10.2 / Num. measured all: 111413 | |||||||||||||||||||||||||||
Reflection shell | Num. unique obs: 874 / Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6DBN Resolution: 2.11→73.38 Å / Cor.coef. Fo:Fc: 0.943 / Cor.coef. Fo:Fc free: 0.93 / SU R Cruickshank DPI: 0.224 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.221 / SU Rfree Blow DPI: 0.173 / SU Rfree Cruickshank DPI: 0.175
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Displacement parameters | Biso max: 123.85 Å2 / Biso mean: 46.18 Å2 / Biso min: 20.83 Å2
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Refine analyze | Luzzati coordinate error obs: 0.28 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.11→73.38 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.11→2.24 Å / Rfactor Rfree error: 0 / Total num. of bins used: 9
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Refinement TLS params. | Method: refined / Origin x: 10.4202 Å / Origin y: 4.3892 Å / Origin z: -16.844 Å
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Refinement TLS group | Selection details: { A|* } |