+Open data
-Basic information
Entry | Database: PDB / ID: 8eqd | ||||||
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Title | Co-crystal structure of PERK with compound 24 | ||||||
Components | Eukaryotic translation initiation factor 2-alpha kinase 3 | ||||||
Keywords | TRANSFERASE / kinase / PERK / inhibitor | ||||||
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 / ER overload response / positive regulation of transcription by RNA polymerase I / 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 / Signaling by ALK fusions and activated point mutants / 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 / 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 / endoplasmic reticulum membrane / positive regulation of gene expression / perinuclear region of cytoplasm / enzyme binding / endoplasmic reticulum / ATP binding / membrane / identical protein binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.92 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 | 8eqd.cif.gz | 72.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8eqd.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8eqd.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/eq/8eqd ftp://data.pdbj.org/pub/pdb/validation_reports/eq/8eqd | HTTPS FTP |
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-Related structure data
Related structure data | 8eq9C 8eqeC 4x7jS C: citing same article (ref.) S: Starting model for refinement |
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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-WPX / ( |
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: 3.43 Å3/Da / Density % sol: 64.15 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop Details: 100 mM HEPES pH 7.0, 180 mM Na/K tartrate, 9% PEG3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 1.0332 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 11, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.0332 Å / Relative weight: 1 |
Reflection | Resolution: 2.92→41.51 Å / Num. obs: 10640 / % possible obs: 95.3 % / Redundancy: 6.7 % / CC1/2: 0.997 / Rmerge(I) obs: 0.097 / Net I/σ(I): 9.5 |
Reflection shell | Resolution: 2.92→2.97 Å / Rmerge(I) obs: 0.794 / Num. unique obs: 510 / CC1/2: 0.817 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4X7J Resolution: 2.92→41.51 Å / Cor.coef. Fo:Fc: 0.943 / Cor.coef. Fo:Fc free: 0.938 / SU B: 42.134 / SU ML: 0.584 / Cross valid method: FREE R-VALUE / ESU R: 0.865 / ESU R Free: 0.388 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: 93.984 Å2
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Refinement step | Cycle: LAST / Resolution: 2.92→41.51 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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