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| | ==The structure of BCL6 BTB (POZ) domain in complex with the ansamycin antibiotic rifabutin.== | | ==The structure of BCL6 BTB (POZ) domain in complex with the ansamycin antibiotic rifabutin.== |
| - | <StructureSection load='4cp3' size='340' side='right' caption='[[4cp3]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='4cp3' size='340' side='right'caption='[[4cp3]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4cp3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CP3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CP3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4cp3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CP3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CP3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RBT:RIFABUTIN'>RBT</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</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=4cp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cp3 OCA], [http://pdbe.org/4cp3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cp3 RCSB], [http://www.ebi.ac.uk/pdbsum/4cp3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cp3 ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RBT:RIFABUTIN'>RBT</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4cp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cp3 OCA], [https://pdbe.org/4cp3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cp3 RCSB], [https://www.ebi.ac.uk/pdbsum/4cp3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cp3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == 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. | + | [https://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 == | | == 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> | + | [https://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4cp3" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4cp3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Evans, S E]] | + | [[Category: Large Structures]] |
| - | [[Category: Fairall, L]] | + | [[Category: Evans SE]] |
| - | [[Category: Ferrigno, P K]] | + | [[Category: Fairall L]] |
| - | [[Category: Ford, R]] | + | [[Category: Ferrigno PK]] |
| - | [[Category: Goult, B T]] | + | [[Category: Ford R]] |
| - | [[Category: Jamieson, A G]] | + | [[Category: Goult BT]] |
| - | [[Category: Schwabe, J W.R]] | + | [[Category: Jamieson AG]] |
| - | [[Category: Wagner, S D]] | + | [[Category: Schwabe JWR]] |
| - | [[Category: Antibiotic]]
| + | [[Category: Wagner SD]] |
| - | [[Category: Btb/poz]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Rifamycin]]
| + | |
| - | [[Category: Smrt]]
| + | |
| - | [[Category: Transcriptional repressor]]
| + | |
| Structural highlights
Disease
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
BCL6_HUMAN Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis.[1] [2]
Publication Abstract from PubMed
BCL6 is a transcriptional repressor that is over-expressed due to chromosomal translocations, or other abnormalities, in approximately 40% of diffuse large B-cell lymphoma. BCL6 interacts with co-repressor, SMRT, and this is essential for its role in lymphomas. Peptide or small molecule inhibitors, which prevent the association of SMRT with BCL6, inhibit transcriptional repression and cause apoptosis of lymphoma cells in vitro and in vivo. In order to discover compounds, which have the potential to be developed into BCL6 inhibitors, we screened a natural product library. The ansamycin antibiotic, rifamycin SV, inhibited BCL6 transcriptional repression and NMR spectroscopy confirmed a direct interaction between rifamycin SV and BCL6. To further determine the characteristics of compounds binding to BCL6-POZ we analyzed four other members of this family and showed that rifabutin, bound most strongly. An X-ray crystal structure of the rifabutin-BCL6 complex revealed that rifabutin occupies a partly non-polar pocket making interactions with tyrosine58, asparagine21 and arginine24 of the BCL6-POZ domain. Importantly these residues are also important for the interaction of BLC6 with SMRT. This work demonstrates a unique approach to developing a structure activity relationship for a compound that will form the basis of a therapeutically useful BCL6 inhibitor.
The Ansamycin Antibiotic, Rifamycin SV, Inhibits BCL6 Transcriptional Repression and Forms a Complex with the BCL6-BTB/POZ Domain.,Evans SE, Goult BT, Fairall L, Jamieson AG, Ko Ferrigno P, Ford R, Schwabe JW, Wagner SD PLoS One. 2014 Mar 4;9(3):e90889. doi: 10.1371/journal.pone.0090889. eCollection , 2014. PMID:24595451[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Niu H, Ye BH, Dalla-Favera R. Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor. Genes Dev. 1998 Jul 1;12(13):1953-61. PMID:9649500
- ↑ Ghetu AF, Corcoran CM, Cerchietti L, Bardwell VJ, Melnick A, Prive GG. Structure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer. Mol Cell. 2008 Feb 15;29(3):384-91. PMID:18280243 doi:10.1016/j.molcel.2007.12.026
- ↑ Evans SE, Goult BT, Fairall L, Jamieson AG, Ko Ferrigno P, Ford R, Schwabe JW, Wagner SD. The Ansamycin Antibiotic, Rifamycin SV, Inhibits BCL6 Transcriptional Repression and Forms a Complex with the BCL6-BTB/POZ Domain. PLoS One. 2014 Mar 4;9(3):e90889. doi: 10.1371/journal.pone.0090889. eCollection , 2014. PMID:24595451 doi:http://dx.doi.org/10.1371/journal.pone.0090889
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