6bpy: Difference between revisions

Latest revision as of 14:48, 4 October 2023

Aspergillus fumigatus Thioredoxin Reductase

Structural highlights

6bpy is a 2 chain structure with sequence from Aspergillus fumigatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.201Å
Ligands:	ACT, FAD, FMT, MLI, MLT, NAP
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A229Y1X4_ASPFM

Publication Abstract from PubMed

Aspergillus fumigatus infections are associated with high mortality rates and high treatment costs. Limited available antifungals and increasing antifungal resistance highlight an urgent need for new antifungals. Thioredoxin reductase (TrxR) is essential for maintaining redox homeostasis and presents as a promising target for novel antifungals. We show that ebselen [2-phenyl-1,2-benzoselenazol-3(2H)-one] is an inhibitor of A. fumigatus TrxR (Ki = 0.22 muM) and inhibits growth of Aspergillus spp., with in vitro MIC values of 16 to 64 microg/ml. Mass spectrometry analysis demonstrates that ebselen interacts covalently with a catalytic cysteine of TrxR, Cys148. We also present the X-ray crystal structure of A. fumigatus TrxR and use in silico modeling of the enzyme-inhibitor complex to outline key molecular interactions. This provides a scaffold for future design of potent and selective antifungal drugs that target TrxR, improving the potency of ebselen toward inhbition of A. fumigatus growth.

Structure, Mechanism, and Inhibition of Aspergillus fumigatus Thioredoxin Reductase.,Marshall AC, Kidd SE, Lamont-Friedrich SJ, Arentz G, Hoffmann P, Coad BR, Bruning JB Antimicrob Agents Chemother. 2019 Feb 26;63(3). pii: AAC.02281-18. doi:, 10.1128/AAC.02281-18. Print 2019 Mar. PMID:30642940^[1]

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

References

↑ Marshall AC, Kidd SE, Lamont-Friedrich SJ, Arentz G, Hoffmann P, Coad BR, Bruning JB. Structure, Mechanism, and Inhibition of Aspergillus fumigatus Thioredoxin Reductase. Antimicrob Agents Chemother. 2019 Feb 26;63(3). pii: AAC.02281-18. doi:, 10.1128/AAC.02281-18. Print 2019 Mar. PMID:30642940 doi:https://dx.doi.org/10.1128/AAC.02281-18

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OCA

[1] Marshall AC, Kidd SE, Lamont-Friedrich SJ, Arentz G, Hoffmann P, Coad BR, Bruning JB. Structure, Mechanism, and Inhibition of Aspergillus fumigatus Thioredoxin Reductase. Antimicrob Agents Chemother. 2019 Feb 26;63(3). pii: AAC.02281-18. doi:, 10.1128/AAC.02281-18. Print 2019 Mar. PMID:30642940 doi:https://dx.doi.org/10.1128/AAC.02281-18

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='6bpy' size='340' side='right'caption='[[6bpy]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6bpy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspfm Aspfm]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BPY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6BPY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6bpy]] 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=6BPY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BPY FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=MLT:D-MALATE'>MLT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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]] 3.201&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDV57_04819, CDV58_04527 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=746128 ASPFM])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=MLT:D-MALATE'>MLT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thioredoxin-disulfide_reductase Thioredoxin-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.9 1.8.1.9] </span></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=6bpy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bpy OCA], [https://pdbe.org/6bpy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bpy RCSB], [https://www.ebi.ac.uk/pdbsum/6bpy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bpy 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=6bpy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bpy OCA], [http://pdbe.org/6bpy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bpy RCSB], [http://www.ebi.ac.uk/pdbsum/6bpy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bpy ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/A0A229Y1X4_ASPFM A0A229Y1X4_ASPFM]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Aspfm]]
+[[Category: Aspergillus fumigatus]]
 [[Category: Large Structures]]
-[[Category: Thioredoxin-disulfide reductase]]
+[[Category: Bruning JB]]
-[[Category: Bruning, J B]]
+[[Category: Marshall AC]]
-[[Category: Marshall, A C]]
-[[Category: Dithiol]]
-[[Category: Oxidoreductase]]
-[[Category: Redox homeostasis]]
-[[Category: Rossmann fold]]

6bpy: Difference between revisions

Latest revision as of 14:48, 4 October 2023

Aspergillus fumigatus Thioredoxin Reductase

Structural highlights

Function

Publication Abstract from PubMed

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References

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