7br0: Difference between revisions
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<StructureSection load='7br0' size='340' side='right'caption='[[7br0]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='7br0' size='340' side='right'caption='[[7br0]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7br0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[7br0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_flavus_NRRL3357 Aspergillus flavus NRRL3357]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BR0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BR0 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.003Å</td></tr> | ||
<tr id=' | <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></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=7br0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7br0 OCA], [https://pdbe.org/7br0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7br0 RCSB], [https://www.ebi.ac.uk/pdbsum/7br0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7br0 ProSAT]</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=7br0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7br0 OCA], [https://pdbe.org/7br0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7br0 RCSB], [https://www.ebi.ac.uk/pdbsum/7br0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7br0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/B8NI43_ASPFN B8NI43_ASPFN] | |||
<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: | [[Category: Aspergillus flavus NRRL3357]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Hara | [[Category: Hara K]] | ||
[[Category: Hashimoto | [[Category: Hashimoto H]] | ||
[[Category: Hertweck | [[Category: Hertweck C]] | ||
[[Category: Maeda | [[Category: Maeda N]] | ||
[[Category: Tsunematsu | [[Category: Tsunematsu Y]] | ||
[[Category: Watanabe | [[Category: Watanabe K]] | ||
Latest revision as of 18:26, 29 November 2023
Crystal structure of AclR, a thioredoxin oxidoreductase fold protein carrying the CXXH catalytic motifCrystal structure of AclR, a thioredoxin oxidoreductase fold protein carrying the CXXH catalytic motif
Structural highlights
FunctionPublication Abstract from PubMedEpidithiodiketopiperazines (ETPs) are a class of ecologically and medicinally important cyclodipeptides bearing a reactive transannular disulfide bridge. Aspirochlorine, an antifungal and toxic ETP isolated from Aspergillus oryzae used in sake brewing, deviates from the common ETP scaffold owing to its unusual ring-enlarged disulfide bridge linked to a spiroaminal ring system. Although this disulfide ring system is implicated in the biological activity of ETPs the biochemical basis for this derailment has remained a mystery. Here we report the discovery of a novel oxidoreductase (AclR) that represents the first-in-class enzyme catalyzing both a carbon-sulfur bond migration and spiro-ring formation, and that the acl pathway involves a cryptic acetylation as a prerequisite for the rearrangement. Genetic screening in A. oryzae identified aclR as the candidate for the complex biotransformation, and the aclR-deficient mutant provided the biosynthetic intermediate, unexpectedly harboring an acetyl group. In vitro assays showed that AclR alone promotes 1,2-sulfamyl migration, elimination of the acetoxy group, and spiroaminal formation. AclR features a thioredoxin oxidoreductase fold with a noncanonical CXXH motif that is distinct from the CXXC in the disulfide forming oxidase for the ETP biosynthesis. Crystallographic and mutational analyses of AclR revealed that the CXXH motif is crucial for catalysis, whereas the flavin-adenine dinucleotide is required as a support of the protein fold, and not as a redox cofactor. AclR proved to be a suitable bioinformatics handle to discover a number of related fungal gene clusters that potentially code for the biosynthesis of derailed ETP compounds. Our results highlight a specialized role of the thioredoxin oxidoreductase family enzyme in the ETP pathway and expand the chemical diversity of small molecules bearing an aberrant disulfide pharmacophore. Specialized Flavoprotein Promotes Sulfur Migration and Spiroaminal Formation in Aspirochlorine Biosynthesis.,Tsunematsu Y, Maeda N, Sato M, Hara K, Hashimoto H, Watanabe K, Hertweck C J Am Chem Soc. 2021 Jan 13;143(1):206-213. doi: 10.1021/jacs.0c08879. Epub 2020, Dec 22. PMID:33351612[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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