7qk0
From Proteopedia
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==Crystal structure of human BCL6 BTB domain in complex with compound 12a== | ==Crystal structure of human BCL6 BTB domain in complex with compound 12a== | ||
| - | <StructureSection load='7qk0' size='340' side='right'caption='[[7qk0]]' scene=''> | + | <StructureSection load='7qk0' size='340' side='right'caption='[[7qk0]], [[Resolution|resolution]] 1.96Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QK0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7qk0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QK0 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7qk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qk0 OCA], [https://pdbe.org/7qk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qk0 RCSB], [https://www.ebi.ac.uk/pdbsum/7qk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qk0 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EBL:(2~{S})-10-[[5-chloranyl-2-[(3~{S},5~{R})-3-methyl-5-oxidanyl-piperidin-1-yl]pyrimidin-4-yl]amino]-2-cyclopropyl-3,3-bis(fluoranyl)-7-methyl-2,4-dihydro-1~{H}-[1,4]oxazepino[2,3-c]quinolin-6-one'>EBL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7qk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qk0 OCA], [https://pdbe.org/7qk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qk0 RCSB], [https://www.ebi.ac.uk/pdbsum/7qk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qk0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [[https://www.uniprot.org/uniprot/BCL6_HUMAN 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 == | ||
| + | [[https://www.uniprot.org/uniprot/BCL6_HUMAN BCL6_HUMAN]] Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis.<ref>PMID:9649500</ref> <ref>PMID:18280243</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The transcriptional repressor BCL6 is an oncogenic driver found to be deregulated in lymphoid malignancies. Herein, we report the optimization of our previously reported benzimidazolone molecular glue-type degrader CCT369260 to CCT373566, a highly potent probe suitable for sustained depletion of BCL6 in vivo. We observed a sharp degradation SAR, where subtle structural changes conveyed the ability to induce degradation of BCL6. CCT373566 showed modest in vivo efficacy in a lymphoma xenograft mouse model following oral dosing. | ||
| + | |||
| + | Improved Binding Affinity and Pharmacokinetics Enable Sustained Degradation of BCL6 In Vivo.,Huckvale R, Harnden AC, Cheung KJ, Pierrat OA, Talbot R, Box GM, Henley AT, de Haven Brandon AK, Hallsworth AE, Bright MD, Akpinar HA, Miller DSJ, Tarantino D, Gowan S, Hayes A, Gunnell EA, Brennan A, Davis OA, Johnson LD, de Klerk S, McAndrew C, Le Bihan YV, Meniconi M, Burke R, Kirkin V, van Montfort RLM, Raynaud FI, Rossanese OW, Bellenie BR, Hoelder S J Med Chem. 2022 Jun 2. doi: 10.1021/acs.jmedchem.1c02175. PMID:35653645<ref>PMID:35653645</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7qk0" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Bihan, Y V.Le]] |
| - | [[Category: | + | [[Category: Gunnell, E A]] |
| - | [[Category: | + | [[Category: Montfort, R L.M van]] |
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Transcription]] | ||
Revision as of 16:23, 6 July 2022
Crystal structure of human BCL6 BTB domain in complex with compound 12a
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