5mw2

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

spinqualitylabelsall models 5mw2, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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: U52 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also B-cell lymphoma proteins 3D structures

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