7q7v
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='7q7v' size='340' side='right'caption='[[7q7v]]' scene=''> | + | <StructureSection load='7q7v' size='340' side='right'caption='[[7q7v]], [[Resolution|resolution]] 1.81Å' 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=7Q7V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q7V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7q7v]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Q7V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Q7V 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=7q7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q7v OCA], [https://pdbe.org/7q7v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q7v RCSB], [https://www.ebi.ac.uk/pdbsum/7q7v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q7v 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=9GR:2-chloranyl-4-[[(2R)-2-cyclopropyl-7-methyl-6-oxidanylidene-1,2,3,4-tetrahydro-[1,4]oxazepino[2,3-c]quinolin-10-yl]amino]pyridine-3-carbonitrile'>9GR</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=7q7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7q7v OCA], [https://pdbe.org/7q7v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7q7v RCSB], [https://www.ebi.ac.uk/pdbsum/7q7v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7q7v 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 == | ||
| + | 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<ref>PMID:35657291</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7q7v" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Bihan, Y V.Le]] |
| - | [[Category: Rodrigues | + | [[Category: Montfort, R L.M van]] |
| - | [[Category: | + | [[Category: Rodrigues, M J]] |
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Transcription]] | ||
Revision as of 16:22, 6 July 2022
Crystal structure of human BCL6 BTB domain in complex with compound 12a
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