7q7r | pdb_00007q7r

Crystal structure of human BCL6 BTB domain in complex with compound 1

spinqualitylabelsall models 7q7r, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7q7r is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 9IH, CL 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 To identify new chemical series with enhanced binding affinity to the BTB domain of B-cell lymphoma 6 protein, we targeted a subpocket adjacent to Val18. With no opportunities for strong polar interactions, we focused on attaining close shape complementarity by ring fusion onto our quinolinone lead series. Following exploration of different sized rings, we identified a conformationally restricted core which optimally filled the available space, leading to potent BCL6 inhibitors. Through X-ray structure-guided design, combined with efficient synthetic chemistry to make the resulting novel core structures, a >300-fold improvement in activity was obtained by the addition of seven heavy atoms. Optimizing Shape Complementarity Enables the Discovery of Potent Tricyclic BCL6 Inhibitors.,Davis OA, Cheung KJ, Brennan A, Lloyd MG, Rodrigues MJ, Pierrat OA, Collie GW, Le Bihan YV, Huckvale R, Harnden AC, Varela A, Bright MD, Eve P, Hayes A, Henley AT, Carter MD, McAndrew PC, Talbot R, Burke R, van Montfort RLM, Raynaud FI, Rossanese OW, Meniconi M, Bellenie BR, Hoelder S J Med Chem. 2022 Jun 3. doi: 10.1021/acs.jmedchem.1c02174. PMID:35657291 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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