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Yorodumi- PDB-5nw2: pVHL:EloB:EloC in complex with (2S,4R)-1-((S)-3,3-dimethyl-2-(oxe... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5nw2 | ||||||
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Title | pVHL:EloB:EloC in complex with (2S,4R)-1-((S)-3,3-dimethyl-2-(oxetane-3-carboxamido)butanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 19) | ||||||
Components |
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Keywords | LIGASE / protein complex / ubiquitin ligase / hypoxia inducible factor | ||||||
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: 2.2 Å | ||||||
Model details | pVHL:EloB:EloC in complex with (2S,4R)-1-((S)-3,3-dimethyl-2-(oxetane-3-carboxamido)butanoyl)-4- ...pVHL:EloB:EloC in complex with (2S,4R)-1-((S)-3,3-dimethyl-2-(oxetane-3-carboxamido)butanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 19) | ||||||
Authors | Gadd, M.S. / Soares, P. / Ciulli, A. | ||||||
Funding support | 1items
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Citation | Journal: J. Med. Chem. / Year: 2018 Title: Group-Based Optimization of Potent and Cell-Active Inhibitors of the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase: Structure-Activity Relationships Leading to the Chemical Probe (2S,4R)-1-((S)- ...Title: Group-Based Optimization of Potent and Cell-Active Inhibitors of the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase: Structure-Activity Relationships Leading to the Chemical Probe (2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (VH298). Authors: Soares, P. / Gadd, M.S. / Frost, J. / Galdeano, C. / Ellis, L. / Epemolu, O. / Rocha, S. / Read, K.D. / Ciulli, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5nw2.cif.gz | 566.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5nw2.ent.gz | 467.9 KB | Display | PDB format |
PDBx/mmJSON format | 5nw2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nw/5nw2 ftp://data.pdbj.org/pub/pdb/validation_reports/nw/5nw2 | HTTPS FTP |
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-Related structure data
Related structure data | 5nvvC 5nvwC 5nvxC 5nvyC 5nvzC 5nw0C 5nw1C 1vcbS 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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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
NCS ensembles :
NCS oper:
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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 / Plasmid: pCDFDuet-1 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / 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 / Plasmid: pCDFDuet-1 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / 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 / Plasmid: pHAT4 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P40337 #4: Chemical | ChemComp-9B8 / ( #5: Water | ChemComp-HOH / | |
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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: 2.54 Å3/Da / Density % sol: 51.48 % / Mosaicity: 0.05 ° |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 6.4 / Details: PEG 3350, MgOAc, Sodium cacodylate, DTT |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.9282 Å | |||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Sep 21, 2015 | |||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9282 Å / Relative weight: 1 | |||||||||||||||||||||
Reflection | Resolution: 2.2→49.54 Å / Num. obs: 86260 / % possible obs: 100 % / Redundancy: 9 % / CC1/2: 0.998 / Rmerge(I) obs: 0.12 / Rpim(I) all: 0.042 / Rrim(I) all: 0.128 / Net I/σ(I): 11 | |||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1VCB Resolution: 2.2→49.54 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.94 / SU B: 11.157 / SU ML: 0.153 / SU R Cruickshank DPI: 0.2526 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.253 / ESU R Free: 0.205 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 139.18 Å2 / Biso mean: 41.604 Å2 / Biso min: 15.73 Å2
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Refinement step | Cycle: final / Resolution: 2.2→49.54 Å
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Refine LS restraints |
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Refine LS restraints NCS | Refine-ID: X-RAY DIFFRACTION
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