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Yorodumi- PDB-8cqe: pVHL:EloB:EloC in complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopro... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8cqe | ||||||
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Title | pVHL:EloB:EloC in complex with (2S,4R)-1-((S)-2-(1-Fluorocyclopropane-1-carboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(2-methyl-4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide (Compound 37) | ||||||
Components |
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Keywords | LIGASE / Inhibitor / E3 ligase complex | ||||||
Function / homology | Function and homology information regulation of cellular response to hypoxia / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / transcription elongation factor activity / target-directed miRNA degradation / elongin complex / VCB complex / Replication of the SARS-CoV-1 genome / Cul5-RING ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex ...regulation of cellular response to hypoxia / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / transcription elongation factor activity / target-directed miRNA degradation / elongin complex / VCB complex / Replication of the SARS-CoV-1 genome / Cul5-RING ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / intracellular non-membrane-bounded organelle / SUMOylation of ubiquitinylation proteins / negative regulation of transcription elongation by RNA polymerase II / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / ubiquitin-like ligase-substrate adaptor activity / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / Formation of HIV elongation complex in the absence of HIV Tat / negative regulation of signal transduction / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / negative regulation of TORC1 signaling / RNA Polymerase II Pre-transcription Events / negative regulation of autophagy / transcription corepressor binding / Evasion by RSV of host interferon responses / transcription elongation by RNA polymerase II / transcription initiation at RNA polymerase II promoter / positive regulation of cell differentiation / TP53 Regulates Transcription of DNA Repair Genes / Vif-mediated degradation of APOBEC3G / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / cell morphogenesis / Inactivation of CSF3 (G-CSF) signaling / Regulation of expression of SLITs and ROBOs / ubiquitin-protein transferase activity / transcription corepressor activity / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / protein-macromolecule adaptor activity / Neddylation / Replication of the SARS-CoV-2 genome / cellular response to hypoxia / ubiquitin-dependent protein catabolic process / regulation of gene expression / proteasome-mediated ubiquitin-dependent protein catabolic process / protein-containing complex assembly / DNA-binding transcription factor binding / amyloid fibril formation / molecular adaptor activity / protein stabilization / protein ubiquitination / negative regulation of cell population proliferation / negative regulation of gene expression / ubiquitin protein ligase binding / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / enzyme binding / negative regulation of transcription by RNA polymerase II / endoplasmic reticulum / mitochondrion / proteolysis / nucleoplasm / nucleus / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.85 Å | ||||||
Authors | Casement, R. / Phuong Vu, L. / Ciulli, A. / Gutschow, M. | ||||||
Funding support | United Kingdom, 1items
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Citation | Journal: J.Med.Chem. / Year: 2023 Title: Expanding the Structural Diversity at the Phenylene Core of Ligands for the von Hippel-Lindau E3 Ubiquitin Ligase: Development of Highly Potent Hypoxia-Inducible Factor-1 alpha Stabilizers. Authors: Vu, L.P. / Diehl, C.J. / Casement, R. / Bond, A.G. / Steinebach, C. / Strasek, N. / Bricelj, A. / Perdih, A. / Schnakenburg, G. / Sosic, I. / Ciulli, A. / Gutschow, M. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8cqe.cif.gz | 271.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8cqe.ent.gz | 216.9 KB | Display | PDB format |
PDBx/mmJSON format | 8cqe.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cq/8cqe ftp://data.pdbj.org/pub/pdb/validation_reports/cq/8cqe | HTTPS FTP |
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-Related structure data
Related structure data | 8cqkC 8cqlC 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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2 |
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3 |
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4 |
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Unit cell |
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-Components
#1: Protein | Mass: 11956.372 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ELOB, TCEB2 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q15370 #2: Protein | Mass: 10974.616 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ELOC, TCEB1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q15369 #3: Protein | Mass: 18806.273 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: VHL / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P40337 #4: Chemical | ChemComp-VFO / ( #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.36 Å3/Da / Density % sol: 47.9 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop Details: 0.1 M sodium cacodylate, pH 6.0-6.3, 15-20% polyethylene glycol 3350, 0.2 M magnesium acetate, 10 mM DTT PH range: 6.0-6.3 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.99 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jul 9, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.99 Å / Relative weight: 1 |
Reflection | Resolution: 2.85→181.02 Å / Num. obs: 38541 / % possible obs: 100 % / Redundancy: 25.5 % / CC1/2: 0.987 / Rmerge(I) obs: 0.897 / Rpim(I) all: 0.18 / Rrim(I) all: 0.915 / Χ2: 1.03 / Net I/σ(I): 5.1 / Num. measured all: 984482 |
Reflection shell | Resolution: 2.85→3 Å / % possible obs: 100 % / Redundancy: 25.8 % / Rmerge(I) obs: 4.704 / Num. measured all: 142660 / Num. unique obs: 5521 / CC1/2: 0.465 / Rpim(I) all: 0.938 / Rrim(I) all: 4.798 / Χ2: 0.89 / Net I/σ(I) obs: 1.3 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.85→90.05 Å / SU ML: 0.38 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 32.12 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.85→90.05 Å
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Refine LS restraints |
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LS refinement shell |
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