+Open data
-Basic information
Entry | Database: PDB / ID: 8eq9 | ||||||
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Title | Co-crystal structure of PERK with compound 11 | ||||||
Components | Eukaryotic translation initiation factor 2-alpha kinase 3 | ||||||
Keywords | TRANSFERASE/Inhibitor / kinase / PERK / inhibitor / TRANSFERASE / TRANSFERASE-Inhibitor complex | ||||||
Function / homology | Function and homology information regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation / negative regulation of translation in response to stress / regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / regulation of translational initiation by eIF2 alpha phosphorylation / eiF2alpha phosphorylation in response to endoplasmic reticulum stress / chondrocyte development / eukaryotic translation initiation factor 2alpha kinase activity / response to manganese-induced endoplasmic reticulum stress / negative regulation of translational initiation in response to stress / PERK-mediated unfolded protein response ...regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation / negative regulation of translation in response to stress / regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / regulation of translational initiation by eIF2 alpha phosphorylation / eiF2alpha phosphorylation in response to endoplasmic reticulum stress / chondrocyte development / eukaryotic translation initiation factor 2alpha kinase activity / response to manganese-induced endoplasmic reticulum stress / negative regulation of translational initiation in response to stress / PERK-mediated unfolded protein response / PERK regulates gene expression / negative regulation of myelination / endocrine pancreas development / ALK mutants bind TKIs / endoplasmic reticulum organization / cellular response to cold / positive regulation of transcription by RNA polymerase I / ER overload response / bone mineralization / positive regulation of vascular endothelial growth factor production / cellular response to glucose starvation / endoplasmic reticulum unfolded protein response / negative regulation of translational initiation / cellular response to amino acid starvation / response to endoplasmic reticulum stress / ossification / insulin-like growth factor receptor signaling pathway / skeletal system development / calcium-mediated signaling / Hsp90 protein binding / positive regulation of protein localization to nucleus / activation of cysteine-type endopeptidase activity involved in apoptotic process / KEAP1-NFE2L2 pathway / Signaling by ALK fusions and activated point mutants / peptidyl-serine phosphorylation / protein phosphatase binding / angiogenesis / protein autophosphorylation / negative regulation of translation / non-specific serine/threonine protein kinase / protein kinase activity / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / positive regulation of gene expression / endoplasmic reticulum membrane / perinuclear region of cytoplasm / enzyme binding / endoplasmic reticulum / ATP binding / identical protein binding / membrane / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.86 Å | ||||||
Authors | Zhu, G. / Surman, M.D. / Mulvihill, M.J. | ||||||
Funding support | 1items
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Citation | Journal: Pharmaceutics / Year: 2022 Title: Optimization of a Novel Mandelamide-Derived Pyrrolopyrimidine Series of PERK Inhibitors. Authors: Stokes, M.E. / Surman, M.D. / Calvo, V. / Surguladze, D. / Li, A.H. / Gasparek, J. / Betzenhauser, M. / Zhu, G. / Du, H. / Rigby, A.C. / Mulvihill, M.J. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8eq9.cif.gz | 73.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8eq9.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8eq9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8eq9_validation.pdf.gz | 749.5 KB | Display | wwPDB validaton report |
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Full document | 8eq9_full_validation.pdf.gz | 751.9 KB | Display | |
Data in XML | 8eq9_validation.xml.gz | 11.9 KB | Display | |
Data in CIF | 8eq9_validation.cif.gz | 15.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/eq/8eq9 ftp://data.pdbj.org/pub/pdb/validation_reports/eq/8eq9 | HTTPS FTP |
-Related structure data
Related structure data | 8eqdC 8eqeC 4x7jS 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: 36816.363 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EIF2AK3, PEK, PERK / Production host: Escherichia coli (E. coli) References: UniProt: Q9NZJ5, non-specific serine/threonine protein kinase |
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#2: Chemical | ChemComp-WPB / ( |
#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: 3.7 Å3/Da / Density % sol: 66.76 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / Details: 12% PEG3350, 4% tacsimate pH7.0 |
-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: Apr 22, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.86→55 Å / Num. obs: 12802 / % possible obs: 100 % / Redundancy: 9.6 % / Rmerge(I) obs: 0.126 / Net I/σ(I): 8 |
Reflection shell | Resolution: 2.86→2.93 Å / Rmerge(I) obs: 0.696 / Num. unique obs: 942 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4X7J Resolution: 2.86→54.875 Å / Cor.coef. Fo:Fc: 0.938 / Cor.coef. Fo:Fc free: 0.914 / SU B: 23.721 / SU ML: 0.375 / Cross valid method: FREE R-VALUE / ESU R: 0.544 / ESU R Free: 0.34 Details: Hydrogens have been added in their 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 BULK SOLVENT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 78.336 Å2
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Refinement step | Cycle: LAST / Resolution: 2.86→54.875 Å
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Refine LS restraints |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20
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