[English] 日本語
Yorodumi- PDB-7lzs: Crystal structure of the BCL6 BTB domain in complex with OICR-11029 -
+Open data
-Basic information
Entry | Database: PDB / ID: 7lzs | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of the BCL6 BTB domain in complex with OICR-11029 | ||||||
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 / 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) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.49 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 |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 7lzs.cif.gz | 113.4 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7lzs.ent.gz | 73 KB | Display | PDB format |
PDBx/mmJSON format | 7lzs.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7lzs_validation.pdf.gz | 748.2 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7lzs_full_validation.pdf.gz | 749.3 KB | Display | |
Data in XML | 7lzs_validation.xml.gz | 8.5 KB | Display | |
Data in CIF | 7lzs_validation.cif.gz | 11.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/lz/7lzs ftp://data.pdbj.org/pub/pdb/validation_reports/lz/7lzs | HTTPS FTP |
-Related structure data
Related structure data | 7lweC 7lwfC 7lwgC 7lzqC 1r28S S: Starting model for refinement C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||||||
Unit cell |
| ||||||||||||
Components on special symmetry positions |
|
-Components
#1: Protein | Mass: 14415.693 Da / Num. of mol.: 1 / Fragment: BTB domain, residues 5-129 / 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 |
---|---|
#2: Chemical | ChemComp-YJS / |
#3: Chemical | ChemComp-DMS / |
#4: Chemical | ChemComp-SO4 / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 2.07 Å3/Da / Density % sol: 40.57 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 8% PEG 6000, 0.1 M Na Acetate pH 4.8, and 100 mM AmS04 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 14, 2015 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.486→29.91 Å / Num. obs: 19187 / % possible obs: 99.6 % / Redundancy: 4.4 % / Biso Wilson estimate: 15.4 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.063 / Rpim(I) all: 0.034 / Rrim(I) all: 0.071 / Net I/σ(I): 13.44 |
Reflection shell | Resolution: 1.486→1.491 Å / Rmerge(I) obs: 0.063 / Mean I/σ(I) obs: 2.36 / Num. unique obs: 190 / CC1/2: 0.814 / Rpim(I) all: 0.35 / Rrim(I) all: 0.74 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1R28 Resolution: 1.49→29.91 Å / SU ML: 0.1801 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 20.7392 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 23.55 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.49→29.91 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
|