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Yorodumi- PDB-6ton: Crystal structure of human BCL6 BTB domain in complex with compou... -
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-Basic information
Entry | Database: PDB / ID: 6ton | ||||||
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Title | Crystal structure of human BCL6 BTB domain in complex with compound 25b | ||||||
Components |
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Keywords | TRANSCRIPTION / Cancer / Lymphoma / Inhibitor / Degrader | ||||||
Function / homology | Function and homology information regulation of memory T cell differentiation / negative regulation of mitotic cell cycle DNA replication / intronic transcription regulatory region sequence-specific DNA binding / negative regulation of isotype switching to IgE isotypes / negative regulation of plasma cell differentiation / negative regulation of T-helper 2 cell differentiation / isotype switching to IgE isotypes / negative regulation of mast cell cytokine production / regulation of germinal center formation / negative regulation of mononuclear cell proliferation ...regulation of memory T cell differentiation / negative regulation of mitotic cell cycle DNA replication / intronic transcription regulatory region sequence-specific DNA binding / negative regulation of isotype switching to IgE isotypes / negative regulation of plasma cell differentiation / negative regulation of T-helper 2 cell differentiation / isotype switching to IgE isotypes / negative regulation of mast cell cytokine production / regulation of germinal center formation / negative regulation of mononuclear cell proliferation / plasma cell differentiation / paraspeckles / germinal center formation / regulation of immune system process / pyramidal neuron differentiation / type 2 immune response / T-helper 2 cell differentiation / positive regulation of regulatory T cell differentiation / negative regulation of B cell apoptotic process / positive regulation of cell motility / FOXO-mediated transcription of cell death genes / negative regulation of Rho protein signal transduction / negative regulation of cell-matrix adhesion / regulation of T cell proliferation / negative regulation of Notch signaling pathway / regulation of cell differentiation / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / B cell proliferation / negative regulation of cellular senescence / Rho protein signal transduction / regulation of immune response / erythrocyte development / positive regulation of B cell proliferation / regulation of cytokine production / positive regulation of neuron differentiation / cell-matrix adhesion / transcription corepressor binding / cell motility / cell morphogenesis / heterochromatin formation / negative regulation of cell growth / chromatin DNA binding / DNA-binding transcription repressor activity, RNA polymerase II-specific / sequence-specific double-stranded DNA binding / protein localization / regulation of cell population proliferation / regulation of inflammatory response / actin cytoskeleton organization / spermatogenesis / Interleukin-4 and Interleukin-13 signaling / DNA-binding transcription factor binding / sequence-specific DNA binding / transcription by RNA polymerase II / inflammatory response / positive regulation of apoptotic process / DNA-binding transcription factor activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of DNA-templated transcription / DNA damage response / chromatin binding / nucleolus / Golgi apparatus / negative regulation of transcription by RNA polymerase II / nucleoplasm / identical protein binding / nucleus / metal ion binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) synthetic construct (others) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.36 Å | ||||||
Authors | Rodrigues, M.J. / Le Bihan, Y.-V. / van Montfort, R.L.M. | ||||||
Funding support | United Kingdom, 1items
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Citation | Journal: J.Med.Chem. / Year: 2020 Title: AchievingIn VivoTarget Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders. Authors: Bellenie, B.R. / Cheung, K.J. / Varela, A. / Pierrat, O.A. / Collie, G.W. / Box, G.M. / Bright, M.D. / Gowan, S. / Hayes, A. / Rodrigues, M.J. / Shetty, K.N. / Carter, M. / Davis, O.A. / ...Authors: Bellenie, B.R. / Cheung, K.J. / Varela, A. / Pierrat, O.A. / Collie, G.W. / Box, G.M. / Bright, M.D. / Gowan, S. / Hayes, A. / Rodrigues, M.J. / Shetty, K.N. / Carter, M. / Davis, O.A. / Henley, A.T. / Innocenti, P. / Johnson, L.D. / Liu, M. / de Klerk, S. / Le Bihan, Y.V. / Lloyd, M.G. / McAndrew, P.C. / Shehu, E. / Talbot, R. / Woodward, H.L. / Burke, R. / Kirkin, V. / van Montfort, R.L.M. / Raynaud, F.I. / Rossanese, O.W. / Hoelder, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6ton.cif.gz | 73.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6ton.ent.gz | 54 KB | Display | PDB format |
PDBx/mmJSON format | 6ton.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6ton_validation.pdf.gz | 824.4 KB | Display | wwPDB validaton report |
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Full document | 6ton_full_validation.pdf.gz | 824.7 KB | Display | |
Data in XML | 6ton_validation.xml.gz | 8.5 KB | Display | |
Data in CIF | 6ton_validation.cif.gz | 11.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/to/6ton ftp://data.pdbj.org/pub/pdb/validation_reports/to/6ton | HTTPS FTP |
-Related structure data
Related structure data | 6tofC 6togC 6tohC 6toiC 6tojC 6tokC 6tolC 6tomC 6tooC 3bimS 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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Unit cell |
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-Components
#1: Protein | Mass: 14536.915 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BCL6, BCL5, LAZ3, ZBTB27, ZNF51 / Plasmid: pET48b / Production host: Escherichia coli BL21 (bacteria) / Variant (production host): AI / References: UniProt: P41182 | ||||
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#2: Protein/peptide | Mass: 655.784 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) | ||||
#3: Chemical | ChemComp-NR5 / | ||||
#4: Chemical | #5: Water | ChemComp-HOH / | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.73 Å3/Da / Density % sol: 67.05 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 2 microliter of the BCL6-BTB/WVIP complex at 4 mg/mL plus 1 microliter of a crystallisation solution consisting of 1 M K2HPO4, 0.7 M NaH2PO4, 75 mM sodium acetate buffer pH 4.5 and 2 % DMSO, ...Details: 2 microliter of the BCL6-BTB/WVIP complex at 4 mg/mL plus 1 microliter of a crystallisation solution consisting of 1 M K2HPO4, 0.7 M NaH2PO4, 75 mM sodium acetate buffer pH 4.5 and 2 % DMSO, against 350 microliter of crystallisation solution. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: MASSIF-1 / Wavelength: 0.966 Å | ||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS3 2M / Detector: PIXEL / Date: Mar 17, 2018 | ||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.966 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||
Reflection | Resolution: 2.36→48.17 Å / Num. obs: 10122 / % possible obs: 99.8 % / Redundancy: 14.5 % / Biso Wilson estimate: 46.2 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.3 / Rpim(I) all: 0.08 / Rrim(I) all: 0.311 / Net I/σ(I): 7.6 / Num. measured all: 146662 / Scaling rejects: 29 | ||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3BIM Resolution: 2.36→40.7 Å / Cor.coef. Fo:Fc: 0.942 / Cor.coef. Fo:Fc free: 0.93 / SU R Cruickshank DPI: 0.212 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.244 / SU Rfree Blow DPI: 0.197 / SU Rfree Cruickshank DPI: 0.185
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Displacement parameters | Biso max: 115.99 Å2 / Biso mean: 46.66 Å2 / Biso min: 22.32 Å2
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Refine analyze | Luzzati coordinate error obs: 0.3 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.36→40.7 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.36→2.39 Å / Rfactor Rfree error: 0 / Total num. of bins used: 26
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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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