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| | <StructureSection load='6y39' size='340' side='right'caption='[[6y39]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='6y39' size='340' side='right'caption='[[6y39]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6y39]] is a 11 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspergillus_nidulans Aspergillus nidulans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y39 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Y39 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6y39]] is a 11 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_nidulans_FGSC_A4 Aspergillus nidulans FGSC A4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Y39 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y39 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g91|4g91]], [[4g92|4g92]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANIA_07545 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227321 Aspergillus nidulans]), ANIA_04034 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227321 Aspergillus nidulans]), AN6492.2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227321 Aspergillus nidulans])</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=6y39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y39 OCA], [https://pdbe.org/6y39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y39 RCSB], [https://www.ebi.ac.uk/pdbsum/6y39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y39 ProSAT]</span></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=6y39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y39 OCA], [http://pdbe.org/6y39 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6y39 RCSB], [http://www.ebi.ac.uk/pdbsum/6y39 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6y39 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/G5EAZ0_EMENI G5EAZ0_EMENI] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aspergillus nidulans]] | + | [[Category: Aspergillus nidulans FGSC A4]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Groll, M]] | + | [[Category: Groll M]] |
| - | [[Category: Huber, E M]] | + | [[Category: Huber EM]] |
| - | [[Category: Heterotrimer]]
| + | |
| - | [[Category: Histone fold]]
| + | |
| - | [[Category: Protein:dna complex]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| Structural highlights
Function
G5EAZ0_EMENI
Publication Abstract from PubMed
Azoles are first-line therapeutics for human and plant fungal infections, but their broad use has promoted the development of resistances. Recently, a pan-azole-resistant clinical Aspergillus fumigatus isolate was identified to carry the mutation P88L in subunit HapE of the CCAAT-binding complex (CBC), a conserved eukaryotic transcription factor. Here, we define the mechanistic basis for resistance in this isolate by showing that the HapE(P88L) mutation interferes with the CBC's ability to bend and sense CCAAT motifs. This failure leads to transcriptional derepression of the cyp51A gene, which encodes the target of azoles, the 14-alpha sterol demethylase Cyp51A, and ultimately causes drug resistance. In addition, we demonstrate that the CBC-associated transcriptional regulator HapX assists cyp51A repression in low-iron environments and that this iron-dependent effect is lost in the HapE(P88L) mutant. Altogether, these results indicate that the mutation HapE(P88L) confers increased resistance to azoles compared with wt A. fumigatus, particularly in low-iron clinical niches such as the lung.
Structural basis of HapE(P88L)-linked antifungal triazole resistance in Aspergillus fumigatus.,Hortschansky P, Misslinger M, Morl J, Gsaller F, Bromley MJ, Brakhage AA, Groll M, Haas H, Huber EM Life Sci Alliance. 2020 May 28;3(7). pii: 3/7/e202000729. doi:, 10.26508/lsa.202000729. Print 2020 Jul. PMID:32467317[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hortschansky P, Misslinger M, Morl J, Gsaller F, Bromley MJ, Brakhage AA, Groll M, Haas H, Huber EM. Structural basis of HapE(P88L)-linked antifungal triazole resistance in Aspergillus fumigatus. Life Sci Alliance. 2020 May 28;3(7). pii: 3/7/e202000729. doi:, 10.26508/lsa.202000729. Print 2020 Jul. PMID:32467317 doi:http://dx.doi.org/10.26508/lsa.202000729
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