5x4q
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the BCL6 BTB domain in complex with Compound 7== | |
| + | <StructureSection load='5x4q' size='340' side='right' caption='[[5x4q]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5x4q]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X4Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X4Q FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7Z6:5-[[5-CHLORANYL-2-(PYRIDIN-3-YLMETHYLAMINO)PYRIMIDIN-4-YL]AMINO]-1,3-DIHYDROINDOL-2-ONE'>7Z6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5x4m|5x4m]], [[5x4n|5x4n]], [[5x4o|5x4o]], [[5x4p|5x4p]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5x4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x4q OCA], [http://pdbe.org/5x4q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x4q RCSB], [http://www.ebi.ac.uk/pdbsum/5x4q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x4q ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/BCL6_HUMAN BCL6_HUMAN]] Note=Chromosomal aberrations involving BCL6 may be a cause of B-cell non-Hodgkin lymphoma. Translocation t(3;14)(q27;q32); translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1. Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF. | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/BCL6_HUMAN BCL6_HUMAN]] Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis.<ref>PMID:9649500</ref> <ref>PMID:18280243</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | B-cell lymphoma 6 (BCL6) is a transcriptional factor that expresses in lymphocytes and regulates the differentiation and proliferation of lymphocytes. Therefore, BCL6 is a therapeutic target for autoimmune diseases and cancer treatment. This report presents the discovery of BCL6-corepressor interaction inhibitors by using a biophysics-driven fragment-based approach. Using the surface plasmon resonance (SPR)-based fragment screening, we successfully identified fragment 1 (SPR KD = 1200 muM, ligand efficiency (LE) = 0.28), a competitive binder to the natural ligand BCoR peptide. Moreover, we elaborated 1 into the more potent compound 7 (SPR KD = 0.078 muM, LE = 0.37, cell-free protein-protein interaction (PPI) IC50 = 0.48 muM (ELISA), cellular PPI IC50 = 8.6 muM (M2H)) by a structure-based design and structural integration with a second high-throughput screening hit. | ||
| - | + | Discovery of a B-Cell Lymphoma 6 Protein-Protein Interaction Inhibitor by a Biophysics-Driven Fragment-Based Approach.,Kamada Y, Sakai N, Sogabe S, Ida K, Oki H, Sakamoto K, Lane W, Snell G, Iida M, Imaeda Y, Sakamoto J, Matsui J J Med Chem. 2017 May 11. doi: 10.1021/acs.jmedchem.7b00313. PMID:28471657<ref>PMID:28471657</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5x4q" style="background-color:#fffaf0;"></div> | |
| - | + | == References == | |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Ida, K]] | [[Category: Ida, K]] | ||
| + | [[Category: Lane, W]] | ||
| + | [[Category: Snell, G]] | ||
[[Category: Sogabe, S]] | [[Category: Sogabe, S]] | ||
| + | [[Category: Transcription repressor]] | ||
| + | [[Category: Transcription-inhibitor complex]] | ||
Revision as of 13:36, 24 May 2017
Crystal structure of the BCL6 BTB domain in complex with Compound 7
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