5x9o

From Proteopedia

Crystal structure of the BCL6 BTB domain in complex with Compound 1a

PDB ID 5x9o

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Structural highlights

5x9o 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 1.58Å
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

B-cell lymphoma 6 (BCL6) is a transcriptional repressor that can form complexes with corepressors via protein-protein interactions (PPIs). The complexes of BCL6 and corepressors play an important role in the formation of germinal centers (GCs), and differentiation and proliferation of lymphocytes. Therefore, BCL6-corepressor interaction inhibitors would be drug candidates for managing autoimmune diseases and cancer. Starting from high-throughput screening hits 1a and 2a, we identified a novel BCL6-corepressor interaction inhibitor 8c (cell-free enzyme-linked immunosorbent assay [ELISA] IC50=0.10microM, cell-based mammalian two-hybrid [M2H] assay IC50=0.72microM) by utilizing structure-based drug design (SBDD) based on an X-ray crystal structure of 1a bound to BCL6. Compound 8c also showed a good pharmacokinetic profile, which was acceptable for both in vitro and in vivo studies.

Discovery of a novel B-cell lymphoma 6 (BCL6)-corepressor interaction inhibitor by utilizing structure-based drug design.,Yasui T, Yamamoto T, Sakai N, Asano K, Takai T, Yoshitomi Y, Davis M, Takagi T, Sakamoto K, Sogabe S, Kamada Y, Lane W, Snell G, Iwata M, Goto M, Inooka H, Sakamoto JI, Nakada Y, Imaeda Y Bioorg Med Chem. 2017 Sep 1;25(17):4876-4886. doi: 10.1016/j.bmc.2017.07.037., Epub 2017 Jul 20. PMID:28760529^[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
↑ Yasui T, Yamamoto T, Sakai N, Asano K, Takai T, Yoshitomi Y, Davis M, Takagi T, Sakamoto K, Sogabe S, Kamada Y, Lane W, Snell G, Iwata M, Goto M, Inooka H, Sakamoto JI, Nakada Y, Imaeda Y. Discovery of a novel B-cell lymphoma 6 (BCL6)-corepressor interaction inhibitor by utilizing structure-based drug design. Bioorg Med Chem. 2017 Sep 1;25(17):4876-4886. doi: 10.1016/j.bmc.2017.07.037., Epub 2017 Jul 20. PMID:28760529 doi:http://dx.doi.org/10.1016/j.bmc.2017.07.037

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

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5x9o

From Proteopedia

Crystal structure of the BCL6 BTB domain in complex with Compound 1a

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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