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5n18

From Proteopedia

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Current revision

Second Bromodomain (BD2) from Candida albicans Bdf1 bound to an imidazopyridine (compound 2)

Structural highlights

5n18 is a 2 chain structure with sequence from Candida albicans SC5314. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.45Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).

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^[1]

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

References

↑ 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. Selective BET bromodomain inhibition as an antifungal therapeutic strategy. Nat Commun. 2017 May 18;8:15482. doi: 10.1038/ncomms15482. PMID:28516956 doi:http://dx.doi.org/10.1038/ncomms15482

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5n18"

@@ Line 3: / Line 3: @@
 <StructureSection load='5n18' size='340' side='right'caption='[[5n18]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5n18]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N18 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5N18 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5n18]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_albicans_SC5314 Candida albicans SC5314]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N18 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N18 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8HZ:4-[8-methyl-3-[(4-methylphenyl)amino]imidazo[1,2-a]pyridin-2-yl]phenol'>8HZ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.45&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5n18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n18 OCA], [http://pdbe.org/5n18 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n18 RCSB], [http://www.ebi.ac.uk/pdbsum/5n18 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n18 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8HZ:4-[8-methyl-3-[(4-methylphenyl)amino]imidazo[1,2-a]pyridin-2-yl]phenol'>8HZ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5n18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n18 OCA], [https://pdbe.org/5n18 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n18 RCSB], [https://www.ebi.ac.uk/pdbsum/5n18 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n18 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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).
+[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 ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Candida albicans SC5314]]
 [[Category: Large Structures]]
-[[Category: Champleboux, M]]
+[[Category: Champleboux M]]
-[[Category: Chauvel, M]]
+[[Category: Chauvel M]]
-[[Category: Cornet, M]]
+[[Category: Cornet M]]
-[[Category: Courcon, M]]
+[[Category: Courcon M]]
-[[Category: Enfert, C d]]
+[[Category: Ferri E]]
-[[Category: Ferri, E]]
+[[Category: Garnaud C]]
-[[Category: Garnaud, C]]
+[[Category: Govin J]]
-[[Category: Govin, J]]
+[[Category: Harbut M]]
-[[Category: Harbut, M]]
+[[Category: Hull M]]
-[[Category: Hull, M]]
+[[Category: Kashemirov BA]]
-[[Category: Kashemirov, B A]]
+[[Category: Maubon D]]
-[[Category: Maubon, D]]
+[[Category: McKenna CE]]
-[[Category: McKenna, C E]]
+[[Category: Mietton F]]
-[[Category: Mietton, F]]
+[[Category: Petosa C]]
-[[Category: Petosa, C]]
+[[Category: Spittler D]]
-[[Category: Spittler, D]]
+[[Category: Zala N]]
-[[Category: Zala, N]]
+[[Category: Zhou Y]]
-[[Category: Zhou, Y]]
+[[Category: D'Enfert C]]
-[[Category: Bromodomain]]
-[[Category: Transcription]]

5n18

From Proteopedia

Current revision

Second Bromodomain (BD2) from Candida albicans Bdf1 bound to an imidazopyridine (compound 2)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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