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Yorodumi- PDB-4x7o: Co-crystal Structure of PERK bound to 1-[5-(4-amino-2,7-dimethyl-... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4x7o | ||||||
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Title | Co-crystal Structure of PERK bound to 1-[5-(4-amino-2,7-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydro-1H-indol-1-yl]-2-[3-fluoro-5-(trifluoromethyl)phenyl]ethanone inhibitor | ||||||
Components | Eukaryotic translation initiation factor 2-alpha kinase 3,Eukaryotic translation initiation factor 2-alpha kinase 3 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / CATALYTIC DOMAIN / TRANSFERASE-TRANSFERASE INHIBITOR / COMPLEX / 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: 2.65 Å | ||||||
Authors | Shaffer, P.L. / Long, A.M. / Chen, H. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2015 Title: Discovery of 1H-Pyrazol-3(2H)-ones as Potent and Selective Inhibitors of Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK). Authors: Smith, A.L. / Andrews, K.L. / Beckmann, H. / Bellon, S.F. / Beltran, P.J. / Booker, S. / Chen, H. / Chung, Y.A. / D'Angelo, N.D. / Dao, J. / Dellamaggiore, K.R. / Jaeckel, P. / Kendall, R. / ...Authors: Smith, A.L. / Andrews, K.L. / Beckmann, H. / Bellon, S.F. / Beltran, P.J. / Booker, S. / Chen, H. / Chung, Y.A. / D'Angelo, N.D. / Dao, J. / Dellamaggiore, K.R. / Jaeckel, P. / Kendall, R. / Labitzke, K. / Long, A.M. / Materna-Reichelt, S. / Mitchell, P. / Norman, M.H. / Powers, D. / Rose, M. / Shaffer, P.L. / Wu, M.M. / Lipford, J.R. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4x7o.cif.gz | 122.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4x7o.ent.gz | 93.9 KB | Display | PDB format |
PDBx/mmJSON format | 4x7o.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4x7o_validation.pdf.gz | 721.8 KB | Display | wwPDB validaton report |
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Full document | 4x7o_full_validation.pdf.gz | 722.5 KB | Display | |
Data in XML | 4x7o_validation.xml.gz | 11.4 KB | Display | |
Data in CIF | 4x7o_validation.cif.gz | 14.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x7/4x7o ftp://data.pdbj.org/pub/pdb/validation_reports/x7/4x7o | HTTPS FTP |
-Related structure data
Related structure data | 4x7hC 4x7jSC 4x7kC 4x7lC 4x7nC 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 on special symmetry positions |
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-Components
#1: Protein | Mass: 36816.363 Da / Num. of mol.: 1 / Mutation: D937N, Deletion of 670-874 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-3Z6 / |
#3: Water | ChemComp-HOH / |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.59 Å3/Da / Density % sol: 65.7 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6.5 / Details: 0.15M NaCl, 0.1M MES pH 6.5, 12% PEG-3350 |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 0.99999 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Apr 5, 2012 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.99999 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.65→50 Å / Num. obs: 15481 / % possible obs: 99.7 % / Redundancy: 8.6 % / Rmerge(I) obs: 0.091 / Χ2: 0.992 / Net I/av σ(I): 24.24 / Net I/σ(I): 8.3 / Num. measured all: 132638 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Rejects: _
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4X7J Resolution: 2.65→50 Å / Cor.coef. Fo:Fc: 0.96 / Cor.coef. Fo:Fc free: 0.947 / SU B: 20.021 / SU ML: 0.204 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.308 / ESU R Free: 0.231 / Stereochemistry target values: MAXIMUM LIKELIHOOD / 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: 1.2 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 202.9 Å2 / Biso mean: 93.33 Å2 / Biso min: 51.2 Å2
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Refinement step | Cycle: final / Resolution: 2.65→50 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.651→2.72 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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