3lbz | pdb_00003lbz
Crystal Structure of the BCL6 BTB domain complexed with the small molecule inhibitor 79-6
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] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe BCL6 transcriptional repressor is the most frequently involved oncogene in diffuse large B cell lymphoma (DLBCL). We combined computer-aided drug design with functional assays to identify low-molecular-weight compounds that bind to the corepressor binding groove of the BCL6 BTB domain. One such compound disrupted BCL6/corepressor complexes in vitro and in vivo, and was observed by X-ray crystallography and NMR to bind the critical site within the BTB groove. This compound could induce expression of BCL6 target genes and kill BCL6-positive DLBCL cell lines. In xenotransplantation experiments, the compound was nontoxic and potently suppressed DLBCL tumors in vivo. The compound also killed primary DLBCLs from human patients. A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in vivo.,Cerchietti LC, Ghetu AF, Zhu X, Da Silva GF, Zhong S, Matthews M, Bunting KL, Polo JM, Fares C, Arrowsmith CH, Yang SN, Garcia M, Coop A, Mackerell AD Jr, Prive GG, Melnick A Cancer Cell. 2010 Apr 13;17(4):400-11. PMID:20385364[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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