View source for 6zci


==Crystal structure of BRD4-BD1 in complex with NVS-BET-1==
<StructureSection load='6zci' size='340' side='right'caption='[[6zci]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6zci]] 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=6ZCI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZCI 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]] 1.976&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QFN:(4~{R})-4-(4-chlorophenyl)-1-cyclopropyl-5-(1,5-dimethyl-6-oxidanylidene-pyridin-3-yl)-3-methyl-4~{H}-pyrrolo[3,4-c]pyrazol-6-one'>QFN</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=6zci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zci OCA], [https://pdbe.org/6zci PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zci RCSB], [https://www.ebi.ac.uk/pdbsum/6zci PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zci 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 ==
Although most acute skin wounds heal rapidly, non-healing skin ulcers represent an increasing and substantial unmet medical need that urgently requires effective therapeutics. Keratinocytes resurface wounds to re-establish the epidermal barrier by transitioning to an activated, migratory state, but this ability is lost in dysfunctional chronic wounds. Small-molecule regulators of keratinocyte plasticity with the potential to reverse keratinocyte malfunction in situ could offer a novel therapeutic approach in skin wound healing. Utilizing high-throughput phenotypic screening of primary keratinocytes, we identify such small molecules, including bromodomain and extra-terminal domain (BET) protein family inhibitors (BETi). BETi induce a sustained activated, migratory state in keratinocytes in vitro, increase activation markers in human epidermis ex vivo and enhance skin wound healing in vivo. Our findings suggest potential clinical utility of BETi in promoting keratinocyte re-epithelialization of skin wounds. Importantly, this novel property of BETi is exclusively observed after transient low-dose exposure, revealing new potential for this compound class.

BET bromodomain inhibitors regulate keratinocyte plasticity.,Schutzius G, Kolter C, Bergling S, Tortelli F, Fuchs F, Renner S, Guagnano V, Cotesta S, Rueeger H, Faller M, Bouchez L, Salathe A, Nigsch F, Richards SM, Louis M, Gruber V, Aebi A, Turner J, Grandjean F, Li J, Dimitri C, Thomas JR, Schirle M, Blank J, Drueckes P, Vaupel A, Tiedt R, Manley PW, Klopp J, Hemmig R, Zink F, Leroy N, Carbone W, Roma G, Keller CG, Dales N, Beyerbach A, Zimmerlin A, Bonenfant D, Terranova R, Berwick A, Sahambi S, Reynolds A, Jennings LL, Ruffner H, Tarsa P, Bouwmeester T, Driver V, Frederiksen M, Lohmann F, Kirkland S Nat Chem Biol. 2021 Mar;17(3):280-290. doi: 10.1038/s41589-020-00716-z. Epub 2021 , Jan 18. PMID:33462494<ref>PMID:33462494</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6zci" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Faller M]]