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Yorodumi- PDB-7lzq: Crystal structure of the BCL6 BTB domain in complex with OICR-4425 -
+Open data
-Basic information
Entry | Database: PDB / ID: 7lzq | ||||||
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Title | Crystal structure of the BCL6 BTB domain in complex with OICR-4425 | ||||||
Components | B-cell lymphoma 6 protein | ||||||
Keywords | TRANSCRIPTION/INHIBITOR / immunity / inflammatory response / transcription repressor / TRANSCRIPTION-INHIBITOR complex | ||||||
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 / pyramidal neuron differentiation / regulation of immune system process / type 2 immune response / positive regulation of regulatory T cell differentiation / T-helper 2 cell differentiation / negative regulation of B cell apoptotic process / positive regulation of cell motility / negative regulation of Rho protein signal transduction / FOXO-mediated transcription of cell death genes / negative regulation of cell-matrix adhesion / regulation of T cell proliferation / negative regulation of Notch signaling pathway / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / B cell proliferation / regulation of cell differentiation / negative regulation of cellular senescence / Rho protein signal transduction / regulation of immune response / erythrocyte development / heterochromatin formation / 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 / protein localization / negative regulation of cell growth / chromatin DNA binding / DNA-binding transcription repressor activity, RNA polymerase II-specific / sequence-specific double-stranded DNA binding / 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 / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / 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) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.71 Å | ||||||
Authors | Kuntz, D.A. / Prive, G.G. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2023 Title: Discovery of OICR12694: A Novel, Potent, Selective, and Orally Bioavailable BCL6 BTB Inhibitor. Authors: Mamai, A. / Chau, A.M. / Wilson, B.J. / Watson, I.D. / Joseph, B.B. / Subramanian, P.R. / Morshed, M.M. / Morin, J.A. / Prakesch, M.A. / Lu, T. / Connolly, P. / Kuntz, D.A. / Pomroy, N.C. / ...Authors: Mamai, A. / Chau, A.M. / Wilson, B.J. / Watson, I.D. / Joseph, B.B. / Subramanian, P.R. / Morshed, M.M. / Morin, J.A. / Prakesch, M.A. / Lu, T. / Connolly, P. / Kuntz, D.A. / Pomroy, N.C. / Poda, G. / Nguyen, K. / Marcellus, R. / Strathdee, G. / Theriault, B. / Subramaniam, R. / Mohammed, M. / Abibi, A. / Chan, M. / Winston, J. / Kiyota, T. / Undzys, E. / Aman, A. / Austin, N. / Du Jardin, M. / Packman, K. / Phillippar, U. / Attar, R. / Edwards, J. / O'Meara, J. / Uehling, D.E. / Al-Awar, R. / Prive, G.G. / Isaac, M.B. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7lzq.cif.gz | 76.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7lzq.ent.gz | 51.9 KB | Display | PDB format |
PDBx/mmJSON format | 7lzq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7lzq_validation.pdf.gz | 735.3 KB | Display | wwPDB validaton report |
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Full document | 7lzq_full_validation.pdf.gz | 735.4 KB | Display | |
Data in XML | 7lzq_validation.xml.gz | 8.9 KB | Display | |
Data in CIF | 7lzq_validation.cif.gz | 12.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/lz/7lzq ftp://data.pdbj.org/pub/pdb/validation_reports/lz/7lzq | HTTPS FTP |
-Related structure data
Related structure data | 7lweC 7lwfC 7lwgC 7lzsC 1r28S C: citing same article (ref.) S: Starting model for refinement |
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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 on special symmetry positions |
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-Components
#1: Protein | Mass: 14802.160 Da / Num. of mol.: 1 / Fragment: BTB domain, residues 1-129 / Mutation: C8Q, C67R, C84N Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BCL6, BCL5, LAZ3, ZBTB27, ZNF51 Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: P41182 |
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#2: Chemical | ChemComp-YJV / |
#3: Chemical | ChemComp-DMS / |
#4: 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: 1.95 Å3/Da / Density % sol: 37.06 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop Details: Protein (Bcl6 BTB domain(1-129) 13 mg/ml in protein buffer( 20 mM Tris pH 8.3, 300 mM NaCl, 10% glycerol, 1 mM TECEP)) was mixed 1:1 with reservoir buffer (1.3M sodium formate, 0.1M Na ...Details: Protein (Bcl6 BTB domain(1-129) 13 mg/ml in protein buffer( 20 mM Tris pH 8.3, 300 mM NaCl, 10% glycerol, 1 mM TECEP)) was mixed 1:1 with reservoir buffer (1.3M sodium formate, 0.1M Na acetate pH 5.2. Ostwald ripening of the early appearing crystals took place over about 5 days. To affect a partial dehydration the reservoir buffer was exchanged in 0.5 M steps to 4 M Na formate/0.1M Na acetate pH 5.2. In separate wells drops of soaking buffer ((1 M Na formate, 5% glycerol, 50 mM Na acetate pH5.2, 10 mM Tris pH 8.3, 150 mM NaCl) was also equilibrated against the 4 M formate/acetate. Crystals were transferred to equilibrated soaking buffer to which 2.5 mM OICR-4425 and 5% DMSO had been added. |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.54 Å |
Detector | Type: APEX II CCD / Detector: CCD / Date: May 25, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.54 Å / Relative weight: 1 |
Reflection | Resolution: 1.71→27.21 Å / Num. obs: 12163 / % possible obs: 96.8 % / Redundancy: 3.9 % / Biso Wilson estimate: 16.44 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.026 / Rpim(I) all: 0.015 / Rrim(I) all: 0.03 / Net I/σ(I): 30.7 |
Reflection shell | Resolution: 1.71→1.74 Å / Redundancy: 3 % / Rmerge(I) obs: 0.127 / Mean I/σ(I) obs: 7.6 / Num. unique obs: 1464 / CC1/2: 0.989 / Rpim(I) all: 0.083 / Rrim(I) all: 0.153 / % possible all: 80.5 |
-Processing
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1R28 Resolution: 1.71→27.2 Å / SU ML: 0.2335 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 22.8962 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 23.69 Å2 | |||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.71→27.2 Å
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Refine LS restraints |
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LS refinement shell |
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