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5mw2

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CRYSTAL STRUCTURE OF BCL-6 BTB-domain with BI-3802

Structural highlights

5mw2 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.35Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

The transcription factor BCL6 is a known driver of oncogenesis in lymphoid malignancies, including diffuse large B cell lymphoma (DLBCL). Disruption of its interaction with transcriptional repressors interferes with the oncogenic effects of BCL6. We used a structure-based drug design to develop highly potent compounds that block this interaction. A subset of these inhibitors also causes rapid ubiquitylation and degradation of BCL6 in cells. These compounds display significantly stronger induction of expression of BCL6-repressed genes and anti-proliferative effects than compounds that merely inhibit co-repressor interactions. This work establishes the BTB domain as a highly druggable structure, paving the way for the use of other members of this protein family as drug targets. The magnitude of effects elicited by this class of BCL6-degrading compounds exceeds that of our equipotent non-degrading inhibitors, suggesting opportunities for the development of BCL6-based lymphoma therapeutics.

Chemically Induced Degradation of the Oncogenic Transcription Factor BCL6.,Kerres N, Steurer S, Schlager S, Bader G, Berger H, Caligiuri M, Dank C, Engen JR, Ettmayer P, Fischerauer B, Flotzinger G, Gerlach D, Gerstberger T, Gmaschitz T, Greb P, Han B, Heyes E, Iacob RE, Kessler D, Kolle H, Lamarre L, Lancia DR, Lucas S, Mayer M, Mayr K, Mischerikow N, Muck K, Peinsipp C, Petermann O, Reiser U, Rudolph D, Rumpel K, Salomon C, Scharn D, Schnitzer R, Schrenk A, Schweifer N, Thompson D, Traxler E, Varecka R, Voss T, Weiss-Puxbaum A, Winkler S, Zheng X, Zoephel A, Kraut N, McConnell D, Pearson M, Koegl M Cell Rep. 2017 Sep 19;20(12):2860-2875. doi: 10.1016/j.celrep.2017.08.081. PMID:28930682^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Kerres N, Steurer S, Schlager S, Bader G, Berger H, Caligiuri M, Dank C, Engen JR, Ettmayer P, Fischerauer B, Flotzinger G, Gerlach D, Gerstberger T, Gmaschitz T, Greb P, Han B, Heyes E, Iacob RE, Kessler D, Kolle H, Lamarre L, Lancia DR, Lucas S, Mayer M, Mayr K, Mischerikow N, Muck K, Peinsipp C, Petermann O, Reiser U, Rudolph D, Rumpel K, Salomon C, Scharn D, Schnitzer R, Schrenk A, Schweifer N, Thompson D, Traxler E, Varecka R, Voss T, Weiss-Puxbaum A, Winkler S, Zheng X, Zoephel A, Kraut N, McConnell D, Pearson M, Koegl M. Chemically Induced Degradation of the Oncogenic Transcription Factor BCL6. Cell Rep. 2017 Sep 19;20(12):2860-2875. doi: 10.1016/j.celrep.2017.08.081. PMID:28930682 doi:http://dx.doi.org/10.1016/j.celrep.2017.08.081

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5mw2"

@@ Line 3: / Line 3: @@
 <StructureSection load='5mw2' size='340' side='right'caption='[[5mw2]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5mw2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MW2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MW2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5mw2]] is a 1 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=5MW2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MW2 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U52:2-[6-[[5-chloranyl-2-[(3~{S},5~{R})-3,5-dimethylpiperidin-1-yl]pyrimidin-4-yl]amino]-1-methyl-2-oxidanylidene-quinolin-3-yl]oxy-~{N}-methyl-ethanamide'>U52</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]] 2.35&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mw2 OCA], [http://pdbe.org/5mw2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mw2 RCSB], [http://www.ebi.ac.uk/pdbsum/5mw2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mw2 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U52:2-[6-[[5-chloranyl-2-[(3~{S},5~{R})-3,5-dimethylpiperidin-1-yl]pyrimidin-4-yl]amino]-1-methyl-2-oxidanylidene-quinolin-3-yl]oxy-~{N}-methyl-ethanamide'>U52</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=5mw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mw2 OCA], [https://pdbe.org/5mw2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mw2 RCSB], [https://www.ebi.ac.uk/pdbsum/5mw2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mw2 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.
+[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 ==
-[[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;">
 == Publication Abstract from PubMed ==
@@ Line 29: / Line 30: @@
 [[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Bader, G]]
+[[Category: Bader G]]
-[[Category: Flotzinger, G]]
+[[Category: Flotzinger G]]
-[[Category: Weiss-Puxbaum, A]]
+[[Category: Weiss-Puxbaum A]]
-[[Category: Zoephel, A]]
+[[Category: Zoephel A]]
-[[Category: Inhibitor]]
-[[Category: Transcription]]

5mw2

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF BCL-6 BTB-domain with BI-3802

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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