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Yorodumi- PDB-4w9e: pVHL:EloB:EloC in complex with (2S,4R)-1-(3,3-dimethylbutanoyl)-4... -
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-Basic information
Entry | Database: PDB / ID: 4w9e | ||||||||||||
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Title | pVHL:EloB:EloC in complex with (2S,4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(thiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 4) | ||||||||||||
Components |
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Keywords | LIGASE / protein complex / ubiquitin ligase / hypoxia inducible factor / transcription | ||||||||||||
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 / transcription initiation at RNA polymerase II promoter / TP53 Regulates Transcription of DNA Repair Genes / positive regulation of cell differentiation / transcription elongation by RNA polymerase II / Vif-mediated degradation of APOBEC3G / cell morphogenesis / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Inactivation of CSF3 (G-CSF) signaling / Evasion by RSV of host interferon responses / 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 / cellular response to hypoxia / regulation of gene expression / Neddylation / protein-macromolecule adaptor activity / Replication of the SARS-CoV-2 genome / DNA-binding transcription factor binding / ubiquitin-dependent protein catabolic process / protein-containing complex assembly / proteasome-mediated ubiquitin-dependent protein catabolic process / 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 transcription by RNA polymerase II / positive regulation of DNA-templated transcription / negative regulation of apoptotic process / 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: 2.6 Å | ||||||||||||
Authors | Gadd, M.S. / Soares, P. / Galdeano, C. / van Molle, I. / Ciulli, A. | ||||||||||||
Funding support | United Kingdom, 3items
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Citation | Journal: J.Med.Chem. / Year: 2014 Title: Structure-Guided Design and Optimization of Small Molecules Targeting the Protein-Protein Interaction between the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor ...Title: Structure-Guided Design and Optimization of Small Molecules Targeting the Protein-Protein Interaction between the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities. Authors: Galdeano, C. / Gadd, M.S. / Soares, P. / Scaffidi, S. / Van Molle, I. / Birced, I. / Hewitt, S. / Dias, D.M. / Ciulli, A. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4w9e.cif.gz | 541.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4w9e.ent.gz | 447.7 KB | Display | PDB format |
PDBx/mmJSON format | 4w9e.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4w9e_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 4w9e_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 4w9e_validation.xml.gz | 47.7 KB | Display | |
Data in CIF | 4w9e_validation.cif.gz | 65.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/w9/4w9e ftp://data.pdbj.org/pub/pdb/validation_reports/w9/4w9e | HTTPS FTP |
-Related structure data
Related structure data | 4w9cC 4w9dC 4w9fC 4w9gC 4w9hC 4w9iC 4w9jC 4w9kC 4w9lC 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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3 |
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4 |
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Unit cell |
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Components on special symmetry positions |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
NCS ensembles :
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Details | The biological unit is a trimer. There are four biological units in the asymmetric unit (chains A, B & C, chains D, E & F, chains G, H & I and chains J, K &L). |
-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: TCEB2 / Plasmid: pCDFDuet-1 / 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: TCEB1 / Plasmid: pCDFDuet-1 / 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 / Plasmid: pHAT4 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P40337 #4: Chemical | ChemComp-3JT / ( #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: 2.36 Å3/Da / Density % sol: 47.99 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 6.3 / 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 / Wavelength: 0.9795 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Apr 27, 2014 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 0.993→93.1 Å / Num. all: 50195 / Num. obs: 50195 / % possible obs: 99.1 % / Redundancy: 8.8 % / Rpim(I) all: 0.038 / Rrim(I) all: 0.119 / Rsym value: 0.105 / Net I/av σ(I): 6.75 / Net I/σ(I): 14.3 / Num. measured all: 442204 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 1VCB Resolution: 2.6→93.1 Å / Cor.coef. Fo:Fc: 0.952 / Cor.coef. Fo:Fc free: 0.923 / WRfactor Rfree: 0.2295 / WRfactor Rwork: 0.1777 / FOM work R set: 0.774 / SU B: 26.848 / SU ML: 0.272 / SU R Cruickshank DPI: 0.8694 / SU Rfree: 0.3307 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.869 / ESU R Free: 0.331 / Stereochemistry target values: MAXIMUM LIKELIHOOD 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 / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 131.89 Å2 / Biso mean: 52.891 Å2 / Biso min: 22.17 Å2
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Refinement step | Cycle: final / Resolution: 2.6→93.1 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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