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Yorodumi- PDB-6hay: Crystal structure of PROTAC 1 in complex with the bromodomain of ... -
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-Basic information
Entry | Database: PDB / ID: 6hay | ||||||
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Title | Crystal structure of PROTAC 1 in complex with the bromodomain of human SMARCA2 and pVHL:ElonginC:ElonginB | ||||||
Components |
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Keywords | GENE REGULATION / bromodomain / E3 Ubiquitin Protein Ligase | ||||||
Function / homology | Function and homology information bBAF complex / npBAF complex / nBAF complex / brahma complex / regulation of cellular response to hypoxia / GBAF complex / regulation of G0 to G1 transition / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / regulation of nucleotide-excision repair ...bBAF complex / npBAF complex / nBAF complex / brahma complex / regulation of cellular response to hypoxia / GBAF complex / regulation of G0 to G1 transition / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / regulation of nucleotide-excision repair / target-directed miRNA degradation / transcription elongation factor activity / elongin complex / VCB complex / Replication of the SARS-CoV-1 genome / regulation of mitotic metaphase/anaphase transition / SWI/SNF complex / Cul5-RING ubiquitin ligase complex / positive regulation of double-strand break repair / ATP-dependent chromatin remodeler activity / positive regulation of T cell differentiation / intermediate filament cytoskeleton / Cul2-RING ubiquitin ligase complex / intracellular non-membrane-bounded organelle / positive regulation of stem cell population maintenance / SUMOylation of ubiquitinylation proteins / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / Regulation of MITF-M-dependent genes involved in pigmentation / negative regulation of transcription elongation by RNA polymerase II / regulation of G1/S transition of mitotic cell cycle / 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 / negative regulation of cell differentiation / spermatid development / ubiquitin-like ligase-substrate adaptor activity / Tat-mediated elongation of the HIV-1 transcript / positive regulation of myoblast differentiation / Formation of HIV-1 elongation complex containing HIV-1 Tat / ATP-dependent activity, acting on DNA / 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 / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / helicase activity / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / positive regulation of cell differentiation / transcription elongation by RNA polymerase II / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / Vif-mediated degradation of APOBEC3G / cell morphogenesis / Inactivation of CSF3 (G-CSF) signaling / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / negative regulation of cell growth / Evasion by RSV of host interferon responses / RMTs methylate histone arginines / Regulation of expression of SLITs and ROBOs / ubiquitin-protein transferase activity / transcription corepressor activity / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Neddylation / nervous system development / Replication of the SARS-CoV-2 genome / protein-macromolecule adaptor activity / histone binding / cellular response to hypoxia / ubiquitin-dependent protein catabolic process / regulation of gene expression / protein-containing complex assembly / proteasome-mediated ubiquitin-dependent protein catabolic process / DNA-binding transcription factor binding / amyloid fibril formation / molecular adaptor activity / transcription coactivator activity / transcription cis-regulatory region binding / protein stabilization / hydrolase activity / protein ubiquitination / chromatin remodeling / negative regulation of cell population proliferation / intracellular membrane-bounded organelle / negative regulation of gene expression / negative regulation of DNA-templated transcription / ubiquitin protein ligase binding / positive regulation of cell population proliferation / chromatin binding / regulation of DNA-templated transcription / negative regulation of apoptotic process / chromatin / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.24 Å | ||||||
Authors | Roy, M. / Bader, G. / Diers, E. / Trainor, N. / Farnaby, W. / Ciulli, A. | ||||||
Funding support | 1items
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Citation | Journal: Nat.Chem.Biol. / Year: 2019 Title: BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design. Authors: Farnaby, W. / Koegl, M. / Roy, M.J. / Whitworth, C. / Diers, E. / Trainor, N. / Zollman, D. / Steurer, S. / Karolyi-Oezguer, J. / Riedmueller, C. / Gmaschitz, T. / Wachter, J. / Dank, C. / ...Authors: Farnaby, W. / Koegl, M. / Roy, M.J. / Whitworth, C. / Diers, E. / Trainor, N. / Zollman, D. / Steurer, S. / Karolyi-Oezguer, J. / Riedmueller, C. / Gmaschitz, T. / Wachter, J. / Dank, C. / Galant, M. / Sharps, B. / Rumpel, K. / Traxler, E. / Gerstberger, T. / Schnitzer, R. / Petermann, O. / Greb, P. / Weinstabl, H. / Bader, G. / Zoephel, A. / Weiss-Puxbaum, A. / Ehrenhofer-Wolfer, K. / Wohrle, S. / Boehmelt, G. / Rinnenthal, J. / Arnhof, H. / Wiechens, N. / Wu, M.Y. / Owen-Hughes, T. / Ettmayer, P. / Pearson, M. / McConnell, D.B. / Ciulli, A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6hay.cif.gz | 407.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6hay.ent.gz | 331.2 KB | Display | PDB format |
PDBx/mmJSON format | 6hay.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6hay_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 6hay_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 6hay_validation.xml.gz | 37.8 KB | Display | |
Data in CIF | 6hay_validation.cif.gz | 53.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ha/6hay ftp://data.pdbj.org/pub/pdb/validation_reports/ha/6hay | HTTPS FTP |
-Related structure data
Related structure data | 6haxC 6hazC 6hr2C 4qy4S 5t35S 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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1 |
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2 |
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Unit cell |
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-Components
-Protein , 4 types, 8 molecules AEBFCGDH
#1: Protein | Mass: 14380.542 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SMARCA2, BAF190B, BRM, SNF2A, SNF2L2 / Plasmid: pDEST15 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) References: UniProt: P51531, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement #2: Protein | Mass: 18702.291 Da / Num. of mol.: 2 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 #3: Protein | Mass: 10974.616 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ELOC, TCEB1 / Plasmid: pCDF-1b DUET / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q15369 #4: Protein | Mass: 11748.406 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ELOB, TCEB2 / Plasmid: pCDF-1b DUET / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q15370 |
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-Non-polymers , 5 types, 326 molecules
#5: Chemical | #6: Chemical | ChemComp-EDO / #7: Chemical | ChemComp-FMT / | #8: Chemical | ChemComp-EPE / | #9: 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: 2.61 Å3/Da / Density % sol: 52.79 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.75 Details: 18% (w/v) PEG 3350, 0.2 M sodium formate, 0.1 M HEPES, pH 7.75 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.91587 Å |
Detector | Type: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Jul 30, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.91587 Å / Relative weight: 1 |
Reflection | Resolution: 2.24→48.33 Å / Num. obs: 105978 / % possible obs: 99.6 % / Redundancy: 6.97 % / Biso Wilson estimate: 52.59 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.081 / Rrim(I) all: 0.088 / Net I/σ(I): 16.1 |
Reflection shell | Resolution: 2.24→2.37 Å / Redundancy: 6.94 % / Rmerge(I) obs: 0.851 / Mean I/σ(I) obs: 2 / Num. unique obs: 16832 / CC1/2: 0.81 / Rrim(I) all: 0.919 / % possible all: 97.9 |
-Phasing
Phasing | Method: molecular replacement | |||||||||
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Phasing MR |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5T35, 4QY4 Resolution: 2.24→48.33 Å / Cor.coef. Fo:Fc: 0.947 / Cor.coef. Fo:Fc free: 0.938 / Rfactor Rfree error: 0 / SU R Cruickshank DPI: 0.252 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.254 / SU Rfree Blow DPI: 0.188 / SU Rfree Cruickshank DPI: 0.19
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Displacement parameters | Biso max: 165.73 Å2 / Biso mean: 55.66 Å2 / Biso min: 25.09 Å2
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Refine analyze | Luzzati coordinate error obs: 0.28 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.24→48.33 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.24→2.3 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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