3LBZ

Crystal Structure of the BCL6 BTB domain complexed with the small molecule inhibitor 79-6

Summary for 3LBZ

• Entry DOI: 10.2210/pdb3lbz/pdb
• Descriptor: B-cell lymphoma 6 protein, N-[(4-bromophenyl)sulfonyl]acetamide, (2R)-2-[(5Z)-5-(5-bromo-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]butanedioic acid, ... (4 entities in total)
• Functional Keywords: transcription regulation, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (By similarity): P41182
• Total number of polymer chains: 2
• Total formula weight: 31047.72

Authors

Ghetu, A.F.,Prive, G.G. (deposition date: 2010-01-08, release date: 2010-04-28, Last modification date: 2023-09-06)

Primary citation

Cerchietti, L.C.,Ghetu, A.F.,Zhu, X.,Da Silva, G.F.,Zhong, S.,Matthews, M.,Bunting, K.L.,Polo, J.M.,Fares, C.,Arrowsmith, C.H.,Yang, S.N.,Garcia, M.,Coop, A.,Mackerell, A.D.,Prive, G.G.,Melnick, A.
A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in vivo.
Cancer Cell, 17:400-411, 2010

PubMed Abstract: The 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.

PubMed: 20385364
DOI: 10.1016/j.ccr.2009.12.050

Experimental method

X-RAY DIFFRACTION (2.3 Å)