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Yorodumi- PDB-4m7i: Crystal Structure of GSK6157 Bound to PERK (R587-R1092, delete A6... -
+Open data
-Basic information
Entry | Database: PDB / ID: 4m7i | ||||||
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Title | Crystal Structure of GSK6157 Bound to PERK (R587-R1092, delete A660-T867) at 2.34A Resolution | ||||||
Components | Eukaryotic translation initiation factor 2-alpha kinase 3 | ||||||
Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / deletion mutant / catalytic domain / 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 / negative regulation of myelination / PERK regulates gene expression / 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 / ossification / 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 / insulin-like growth factor receptor signaling pathway / skeletal system development / calcium-mediated signaling / Hsp90 protein binding / activation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of protein localization to nucleus / KEAP1-NFE2L2 pathway / Signaling by ALK fusions and activated point mutants / peptidyl-serine phosphorylation / protein phosphatase binding / angiogenesis / protein autophosphorylation / non-specific serine/threonine protein kinase / negative regulation of translation / 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 / identical protein binding / membrane / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / Difference density / Resolution: 2.34 Å | ||||||
Authors | Gampe, R.T. / Axten, J.M. | ||||||
Citation | Journal: To be Published Title: Discovery of 5-{4-fluoro-1-[(6-methyl-2-pyridinyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2656157), a Potent and Selective PERK Inhibitor Selected ...Title: Discovery of 5-{4-fluoro-1-[(6-methyl-2-pyridinyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2656157), a Potent and Selective PERK Inhibitor Selected for Preclinical Development Authors: Axten, J.M. / Romeril, S.P. / Shu, A. / Ralph, J. / Medina, J.R. / Feng, Y. / Li, W.H.H. / Grant, S.W. / Heerding, D.A. / Minthorn, E. / Mencken, T. / Gaul, N. / Goetz, A. / Stanley, T. / ...Authors: Axten, J.M. / Romeril, S.P. / Shu, A. / Ralph, J. / Medina, J.R. / Feng, Y. / Li, W.H.H. / Grant, S.W. / Heerding, D.A. / Minthorn, E. / Mencken, T. / Gaul, N. / Goetz, A. / Stanley, T. / Hassell, A.M. / Gampe, R.T. / Atkins, C. / Kumar, R. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4m7i.cif.gz | 68.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4m7i.ent.gz | 48.6 KB | Display | PDB format |
PDBx/mmJSON format | 4m7i.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/m7/4m7i ftp://data.pdbj.org/pub/pdb/validation_reports/m7/4m7i | HTTPS FTP |
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-Related structure data
Related structure data | 4g31S 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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Unit cell |
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-Components
#1: Protein | Mass: 34797.215 Da / Num. of mol.: 1 / Fragment: UNP residues 588-660,869-1093 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-27D / |
#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: 3.35 Å3/Da / Density % sol: 63.25 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 100 mM BTP at pH 7.0 with a 3.5 4.9M linear gradient of ammonium acetate , VAPOR DIFFUSION, HANGING DROP, temperature 277K |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-G / Wavelength: 0.97872 Å |
Detector | Type: RAYONIX MX300HS / Detector: CCD / Date: Oct 20, 2010 |
Radiation | Monochromator: C(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97872 Å / Relative weight: 1 |
Reflection | Resolution: 2.34→48 Å / Num. all: 20797 / Num. obs: 20779 / % possible obs: 99.9 % / Observed criterion σ(I): -3 / Redundancy: 11.8 % / Rmerge(I) obs: 0.05 / Net I/σ(I): 44.5 |
Reflection shell | Resolution: 2.34→2.42 Å / Redundancy: 12 % / Rmerge(I) obs: 0.408 / Mean I/σ(I) obs: 6.9 / Num. unique all: 2032 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: Difference density Starting model: PDB entry 4G31 Resolution: 2.34→29.324 Å / SU ML: 0.35 / σ(F): 1.33 / Phase error: 27.15 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.83 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 60 Å2 / ksol: 0.321 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||
Displacement parameters |
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Refinement step | Cycle: LAST / Resolution: 2.34→29.324 Å
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Refine LS restraints |
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LS refinement shell |
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