4z6i: Difference between revisions
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==Crystal structure of BRD9 bromodomain in complex with a substituted valerolactam quinolone ligand== | ==Crystal structure of BRD9 bromodomain in complex with a substituted valerolactam quinolone ligand== | ||
<StructureSection load='4z6i' size='340' side='right' caption='[[4z6i]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='4z6i' size='340' side='right'caption='[[4z6i]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4z6i]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z6I OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4z6i]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z6I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z6I FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4L3:TERT-BUTYL+[(2R,3S)-1-(1,4-DIMETHYL-2-OXO-1,2-DIHYDROQUINOLIN-7-YL)-6-OXO-2-PHENYLPIPERIDIN-3-YL]CARBAMATE'>4L3</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4L3:TERT-BUTYL+[(2R,3S)-1-(1,4-DIMETHYL-2-OXO-1,2-DIHYDROQUINOLIN-7-YL)-6-OXO-2-PHENYLPIPERIDIN-3-YL]CARBAMATE'>4L3</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=4z6i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z6i OCA], [https://pdbe.org/4z6i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z6i RCSB], [https://www.ebi.ac.uk/pdbsum/4z6i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z6i ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/BRD9_HUMAN BRD9_HUMAN] May play a role in chromatin remodeling and regulation of transcription. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 21: | ||
==See Also== | ==See Also== | ||
*[[Bromodomain-containing protein|Bromodomain-containing protein]] | *[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Arrowsmith CH]] | ||
[[Category: | [[Category: Bountra C]] | ||
[[Category: | [[Category: Brennan PE]] | ||
[[Category: Dixon | [[Category: Clark PGK]] | ||
[[Category: Edwards | [[Category: Dixon DJ]] | ||
[[Category: Fedorov | [[Category: Edwards AM]] | ||
[[Category: Knapp | [[Category: Fedorov O]] | ||
[[Category: Krojer | [[Category: Knapp S]] | ||
[[Category: Newman | [[Category: Krojer T]] | ||
[[Category: Nunez-Alonso | [[Category: Newman JA]] | ||
[[Category: Picaud | [[Category: Nunez-Alonso G]] | ||
[[Category: Picaud S]] | |||
[[Category: Tallant | [[Category: Tallant C]] | ||
[[Category: Vieira | [[Category: Vieira LCC]] | ||
[[Category: | [[Category: Von Delft F]] | ||
Latest revision as of 13:58, 10 January 2024
Crystal structure of BRD9 bromodomain in complex with a substituted valerolactam quinolone ligandCrystal structure of BRD9 bromodomain in complex with a substituted valerolactam quinolone ligand
Structural highlights
FunctionBRD9_HUMAN May play a role in chromatin remodeling and regulation of transcription. Publication Abstract from PubMedThe bromodomain-containing proteins BRD9 and BRD7 are part of the human SWI/SNF chromatin-remodeling complexes BAF and PBAF. To date, no selective inhibitor for BRD7/9 has been reported despite its potential value as a biological tool or as a lead for future therapeutics. The quinolone-fused lactam LP99 is now reported as the first potent and selective inhibitor of the BRD7 and BRD9 bromodomains. Development of LP99 from a fragment hit was expedited through balancing structure-based inhibitor design and biophysical characterization against tractable chemical synthesis: Complexity-building nitro-Mannich/lactamization cascade processes allowed for early structure-activity relationship studies whereas an enantioselective organocatalytic nitro-Mannich reaction enabled the synthesis of the lead scaffold in enantioenriched form and on scale. This epigenetic probe was shown to inhibit the association of BRD7 and BRD9 to acetylated histones in vitro and in cells. Moreover, LP99 was used to demonstrate that BRD7/9 plays a role in regulating pro-inflammatory cytokine secretion. LP99: Discovery and Synthesis of the First Selective BRD7/9 Bromodomain Inhibitor.,Clark PG, Vieira LC, Tallant C, Fedorov O, Singleton DC, Rogers CM, Monteiro OP, Bennett JM, Baronio R, Muller S, Daniels DL, Mendez J, Knapp S, Brennan PE, Dixon DJ Angew Chem Int Ed Engl. 2015 May 18;54(21):6217-21. doi: 10.1002/anie.201501394. , Epub 2015 Apr 13. PMID:25864491[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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