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'''Unreleased structure'''


The entry 24km is ON HOLD  until 2028-03-06
==Crystal structure of the first bromodomain (BD1) of human BRD4 in complex with Nimesulide==
<StructureSection load='24km' size='340' side='right'caption='[[24km]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[24km]] 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=24KM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=24KM 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]] 1.86&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NIM:4-NITRO-2-PHENOXYMETHANESULFONANILIDE'>NIM</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=24km FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=24km OCA], [https://pdbe.org/24km PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=24km RCSB], [https://www.ebi.ac.uk/pdbsum/24km PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=24km 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 ==
The bromodomain and extra-terminal (BET) family of proteins, which regulate chromatin function, is an established potential drug target for treating major diseases such as cancer and inflammatory conditions. There is significant research focused on developing new BET inhibitors with innovative molecular structures to target and modulate the epigenetic mechanisms underlying major diseases, including cancer. Herein, we present the crystal structures of the second bromodomain (BD2) of hBRD2 in complex with the FDA-approved drugs, mefenamic acid (ID8) and nimesulide (NIM), and that of the first bromodomain (BD1) of hBRD4 in complex with nimesulide (NIM). Quantitative binding assays by surface plasmon resonance (SPR) confirmed the substantial binding of these drug molecules to the hBRD2 and hBRD4 bromodomains. Using these crystal structures, a series of ID8 and NIM derivatives with improved affinity relative to the parent compounds was designed and evaluated using SeeSAR (BioSolveIT GmbH). Moreover, molecular dynamics simulations were performed on the selected derivatives of ID8 and NIM against these bromodomains and confirmed the stability of these derivatives' binding throughout the simulations. We propose that the derivatives of the aforementioned parent molecules may be potential inhibitors of the function of hBRD2 and hBRD4.


Authors: Padmanabhan, B., Ashok, S.
BET Bromodomain Targeting by NSAIDs: Structural, Biophysical, and Computational Insights.,Sridhar A, Kandhasami N, Mathur S, Krishnappa G, Thiyagarajan S, Padmanabhan B Proteins. 2026 Jul 15. doi: 10.1002/prot.70154. PMID:42458221<ref>PMID:42458221</ref>


Description: Crystal structure of the first bromodomain (BD1) of human BRD4 in complex with Nimesulide
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Padmanabhan, B]]
<div class="pdbe-citations 24km" style="background-color:#fffaf0;"></div>
[[Category: Ashok, S]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ashok S]]
[[Category: Padmanabhan B]]
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