7c6p: Difference between revisions

Latest revision as of 10:45, 12 March 2025

Bromodomain-containing 4 BD2 in complex with 3',4',7,8- Tetrahydroxyflavonoid

Structural highlights

Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.73Å
Ligands:	SQH
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Bromodomain-containing protein 4 (BRD4) binds acetylated lysine residues on the N-terminal tails of histones through two bromodomains (BD1 and BD2) to regulate gene transcription. Inhibiting one or both of bromodomains resulted in different phenotypes, suggesting BD1 and BD2 may have different functions. Here we report the characterisation of a natural product 3',4',7,8-tetrahydroxyflavone as a novel and potent selective BRD4 inhibitor. The compound is 100-fold more selective for BRD4-BD2 (IC50 = 204 nM) than BRD4-BD1 (IC50=17.9 microM). Co-crystal structures show 3',4',7,8-tetrahydroxyflavone binds to the acetylated lysine binding pocket of BRD4-BD1 or BRD4-BD2, but establishes more interactions with BRD4-BD2 than BRD4-BD1. Our data suggest 3',4',7,8-tetrahydroxyflavone as a potent selective inhibitor of BRD4-BD2 with a novel chemical scaffold. Given its distinct chemical structure from current BRD4 inhibitors, this compound may open the door for a novel class of anti-BRD4 inhibitors by serving as a lead compound.

Discovery of the natural product 3',4',7,8-tetrahydroxyflavone as a novel and potent selective BRD4 bromodomain 2 inhibitor.,Li J, Zou W, Yu K, Liu B, Liang W, Wang L, Lu Y, Jiang Z, Wang A, Zhu J J Enzyme Inhib Med Chem. 2021 Dec;36(1):903-913. doi:, 10.1080/14756366.2021.1906663. PMID:33820450^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Li J, Zou W, Yu K, Liu B, Liang W, Wang L, Lu Y, Jiang Z, Wang A, Zhu J. Discovery of the natural product 3',4',7,8-tetrahydroxyflavone as a novel and potent selective BRD4 bromodomain 2 inhibitor. J Enzyme Inhib Med Chem. 2021 Dec;36(1):903-913. PMID:33820450 doi:10.1080/14756366.2021.1906663

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Li J, Zou W, Yu K, Liu B, Liang W, Wang L, Lu Y, Jiang Z, Wang A, Zhu J. Discovery of the natural product 3',4',7,8-tetrahydroxyflavone as a novel and potent selective BRD4 bromodomain 2 inhibitor. J Enzyme Inhib Med Chem. 2021 Dec;36(1):903-913. PMID:33820450 doi:10.1080/14756366.2021.1906663

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='7c6p' size='340' side='right'caption='[[7c6p]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7c6p]] is a 1 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=7C6P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C6P FirstGlance]. <br>
+<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C6P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C6P FirstGlance]. <br>
 </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.73&#8491;</td></tr>
 <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SQH:2-[3,4-bis(oxidanyl)phenyl]-7,8-bis(oxidanyl)chromen-4-one'>SQH</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=7c6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c6p OCA], [https://pdbe.org/7c6p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c6p RCSB], [https://www.ebi.ac.uk/pdbsum/7c6p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c6p ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
-== Function ==
-[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 28: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
 [[Category: Large Structures]]
 [[Category: Li J]]

7c6p: Difference between revisions

Latest revision as of 10:45, 12 March 2025

Bromodomain-containing 4 BD2 in complex with 3',4',7,8- Tetrahydroxyflavonoid

Structural highlights

Publication Abstract from PubMed

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References

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