View source for 7ytv


==Crystal structure of Aspergillus fumigatus Thioredoxin reductase in complex with auranofin==
<StructureSection load='7ytv' size='340' side='right'caption='[[7ytv]], [[Resolution|resolution]] 3.87&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ytv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YTV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YTV 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]] 3.866&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=7ytv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ytv OCA], [https://pdbe.org/7ytv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ytv RCSB], [https://www.ebi.ac.uk/pdbsum/7ytv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ytv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A229Y1X4_ASPFM A0A229Y1X4_ASPFM] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND: Infections caused by azole-resistant Aspergillus are a rising public health threat with high mortality rates, high treatment costs and limited available antifungals, indicating an urgent need for new antifungals or strategies. Our aim was to investigate antifungal and antibiofilm activities of auranofin, an FDA-approved anti-antirheumatic drug. METHODS: Fungal susceptibility testing for auranofin was carried out by the broth-based microdilution methods. Cell viability treated by auranofin was tested by resazurin dye testing. The synergistic effect of auranofin and antifungal drugs was evaluated using checkboard assay. The inhibitory of biofilms were measured by crystal violet staining. Gene expression level analysis and enzyme activity was investigated with qRT-PCR analysis and DTNB assay. The key amino acid residues in the binding of auranofin with A. fumigatus thioredoxin reductase (AfTrxR) were indicated by structural analyses, site-directed mutagenesis, and microscale thermophoresis (MST) assays. RESULTS: Auranofin has fungicidal activity and in vitro antifungal spectrum including Aspergillus flavus, Aspergillus fumigatus, Aspergillus terreus, Aspergillus niger, even itraconazole (ITC)-resistant A. fumigatus. Additionally, it has antibiofilm activities against ITC-resistant A. fumigatus by reducing the expression level of SomA and MedA. Moreover, we discovered a synergistic effect of auranofin and ITC or amphotericin B against ITC-resistant A. fumigatus. Auranofin downregulated the gene transcription of AfTrxR, and strongly inhibited the enzyme activity of AfTrxR through interacting with residues C145 and C148. CONCLUSIONS: Auranofin has fungicidal and antibiofilm activities in Aspergillus spp. and is also a potentiator of ITC or amphotericin B in vitro.

In vitro antifungal and antibiofilm activities of auranofin against itraconazole-resistant Aspergillus fumigatus.,Chen P, Yang J, Jin Y, Lu C, Feng Z, Gao F, Chen Y, Wang F, Shang Z, Lin W J Mycol Med. 2023 May;33(2):101381. doi: 10.1016/j.mycmed.2023.101381. Epub 2023 , Mar 28. PMID:37037064<ref>PMID:37037064</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ytv" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thioredoxin reductase 3D structures|Thioredoxin reductase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Aspergillus fumigatus]]
[[Category: Large Structures]]
[[Category: Lin W]]