View source for 5n15


==First Bromodomain (BD1) from Candida albicans Bdf1 in the unbound form==
<StructureSection load='5n15' size='340' side='right'caption='[[5n15]], [[Resolution|resolution]] 2.37&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5n15]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_albicans Candida albicans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N15 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]] 2.37&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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=5n15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n15 OCA], [https://pdbe.org/5n15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n15 RCSB], [https://www.ebi.ac.uk/pdbsum/5n15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n15 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BDF1_CANAL BDF1_CANAL] Transcription factor involved in the expression of a broad class of genes including snRNAs. Required for sporulation and DNA-damage repair. Prevents the spreading of SIR silencing at telomeres and protects histone H4, but not H3, from deacetylation (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Invasive fungal infections cause significant morbidity and mortality among immunocompromised individuals, posing an urgent need for new antifungal therapeutic strategies. Here we investigate a chromatin-interacting module, the bromodomain (BD) from the BET family of proteins, as a potential antifungal target in Candida albicans, a major human fungal pathogen. We show that the BET protein Bdf1 is essential in C. albicans and that mutations inactivating its two BDs result in a loss of viability in vitro and decreased virulence in mice. We report small-molecule compounds that inhibit C. albicans Bdf1 with high selectivity over human BDs. Crystal structures of the Bdf1 BDs reveal binding modes for these inhibitors that are sterically incompatible with the human BET-binding pockets. Furthermore, we report a dibenzothiazepinone compound that phenocopies the effects of a Bdf1 BD-inactivating mutation on C. albicans viability. These findings establish BET inhibition as a promising antifungal therapeutic strategy and identify Bdf1 as an antifungal drug target that can be selectively inhibited without antagonizing human BET function.

Selective BET bromodomain inhibition as an antifungal therapeutic strategy.,Mietton F, Ferri E, Champleboux M, Zala N, Maubon D, Zhou Y, Harbut M, Spittler D, Garnaud C, Courcon M, Chauvel M, d'Enfert C, Kashemirov BA, Hull M, Cornet M, McKenna CE, Govin J, Petosa C Nat Commun. 2017 May 18;8:15482. doi: 10.1038/ncomms15482. PMID:28516956<ref>PMID:28516956</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5n15" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Candida albicans]]
[[Category: Large Structures]]
[[Category: Champleboux M]]
[[Category: Chauvel M]]
[[Category: Cornet M]]
[[Category: Courcon M]]
[[Category: Ferri E]]
[[Category: Garnaud C]]
[[Category: Govin J]]
[[Category: Harbut M]]
[[Category: Hull M]]
[[Category: Kashemirov BA]]
[[Category: Maubon D]]
[[Category: McKenna CE]]
[[Category: Mietton F]]
[[Category: Petosa C]]
[[Category: Spittler D]]
[[Category: Zala N]]
[[Category: Zhou Y]]
[[Category: D'Enfert C]]