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Yorodumi- PDB-8bb5: Structure of human WDR5 and pVHL:ElonginC:ElonginB bound to PROTA... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8bb5 | ||||||
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Title | Structure of human WDR5 and pVHL:ElonginC:ElonginB bound to PROTAC with Aryl linker | ||||||
Components |
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Keywords | LIGASE / E3-Ligase / WDR5 / VHL / Elongin | ||||||
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 / MLL3/4 complex / elongin complex / VCB complex / Set1C/COMPASS complex / MLL1/2 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 / MLL3/4 complex / elongin complex / VCB complex / Set1C/COMPASS complex / MLL1/2 complex / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Replication of the SARS-CoV-1 genome / Cardiogenesis / Cul5-RING ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / intracellular non-membrane-bounded organelle / regulation of tubulin deacetylation / histone methyltransferase complex / SUMOylation of ubiquitinylation proteins / Formation of WDR5-containing histone-modifying complexes / negative regulation of transcription elongation by RNA polymerase II / regulation of cell division / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / regulation of embryonic development / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / MLL1 complex / histone acetyltransferase complex / 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 / positive regulation of gluconeogenesis / negative regulation of TORC1 signaling / RNA Polymerase II Pre-transcription Events / methylated histone binding / transcription initiation-coupled chromatin remodeling / negative regulation of autophagy / transcription corepressor binding / skeletal system development / gluconeogenesis / 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 / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / PKMTs methylate histone lysines / cell morphogenesis / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Inactivation of CSF3 (G-CSF) signaling / Evasion by RSV of host interferon responses / RMTs methylate histone arginines / mitotic spindle / Activation of anterior HOX genes in hindbrain development during early embryogenesis / 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 / HATs acetylate histones / protein-macromolecule adaptor activity / Replication of the SARS-CoV-2 genome / histone binding / 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 / regulation of cell cycle / 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 / molecular replacement / Resolution: 2.2 Å | ||||||
Authors | Kraemer, A. / Doelle, A. / Knapp, S. / Structural Genomics Consortium (SGC) | ||||||
Funding support | Canada, 1items
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Citation | Journal: Cell Chem Biol / Year: 2023 Title: Tracking the PROTAC degradation pathway in living cells highlights the importance of ternary complex measurement for PROTAC optimization. Authors: Schwalm, M.P. / Kramer, A. / Dolle, A. / Weckesser, J. / Yu, X. / Jin, J. / Saxena, K. / Knapp, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8bb5.cif.gz | 279.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8bb5.ent.gz | 221.2 KB | Display | PDB format |
PDBx/mmJSON format | 8bb5.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bb/8bb5 ftp://data.pdbj.org/pub/pdb/validation_reports/bb/8bb5 | HTTPS FTP |
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-Related structure data
Related structure data | 7q2jSC 8bb4C 8c13C S: Starting model for refinement 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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Unit cell |
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-Components
-Protein , 4 types, 4 molecules ABCD
#1: Protein | Mass: 11748.406 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ELOB, TCEB2 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15370 |
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#2: Protein | Mass: 11043.678 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ELOC, TCEB1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15369 |
#3: Protein | Mass: 18702.291 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: VHL / Production host: Escherichia coli (E. coli) / References: UniProt: P40337 |
#4: Protein | Mass: 35296.922 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: WDR5, BIG3 / Production host: Escherichia coli (E. coli) / References: UniProt: P61964 |
-Non-polymers , 5 types, 350 molecules
#5: Chemical | ChemComp-SCN / #6: Chemical | ChemComp-Q43 / ~{ | #7: Chemical | ChemComp-EDO / #8: Chemical | ChemComp-K / | #9: Water | ChemComp-HOH / | |
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-Details
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: 2.72 Å3/Da / Density % sol: 54.85 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / Details: 21% PEG 3350, 0.4-1 M KSCN 0.1 M HEPES pH 6.8 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.999998 Å | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 16, 2021 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.999998 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 2.2→49.2 Å / Num. obs: 42660 / % possible obs: 99.8 % / Redundancy: 9.1 % / CC1/2: 0.997 / Rmerge(I) obs: 0.166 / Rpim(I) all: 0.058 / Rrim(I) all: 0.176 / Net I/σ(I): 10.1 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR | Model details: Phaser MODE: MR_AUTO
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 7Q2J Resolution: 2.2→49.2 Å / Cor.coef. Fo:Fc: 0.95 / Cor.coef. Fo:Fc free: 0.927 / WRfactor Rfree: 0.231 / WRfactor Rwork: 0.1844 / FOM work R set: 0.7644 / SU B: 14.294 / SU ML: 0.177 / SU R Cruickshank DPI: 0.2456 / SU Rfree: 0.2051 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.246 / ESU R Free: 0.205 / 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: 94.65 Å2 / Biso mean: 34.401 Å2 / Biso min: 20.6 Å2
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Refinement step | Cycle: final / Resolution: 2.2→49.2 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.2→2.257 Å / Rfactor Rfree error: 0 / 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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