7nc3: Difference between revisions
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==Glutathione-S-transferase GliG (space group P212121)== | ==Glutathione-S-transferase GliG (space group P212121)== | ||
<StructureSection load='7nc3' size='340' side='right'caption='[[7nc3]]' scene=''> | <StructureSection load='7nc3' size='340' side='right'caption='[[7nc3]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NC3 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7nc3]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspfc Aspfc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NC3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NC3 FirstGlance]. <br> | ||
</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=7nc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nc3 OCA], [https://pdbe.org/7nc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nc3 RCSB], [https://www.ebi.ac.uk/pdbsum/7nc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nc3 ProSAT]</span></td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7nc1|7nc1]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AFUB_075740 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=451804 ASPFC])</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=7nc3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nc3 OCA], [https://pdbe.org/7nc3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nc3 RCSB], [https://www.ebi.ac.uk/pdbsum/7nc3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nc3 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Glutathione-S-transferases (GSTs) usually detoxify xenobiotics. The human pathogenic fungus Aspergillus fumigatus however uses the exceptional GST GliG to incorporate two sulphur atoms into its virulence factor gliotoxin. Because these sulphurs are essential for biological activity, glutathionylation is a key step of gliotoxin biosynthesis. Yet, the mechanism of carbon-sulphur linkage formation from a bis-hydroxylated precursor is unresolved. Here, we report structures of GliG with glutathione (GSH) and its reaction product cyclo[-l-Phe-l-Ser]-bis-glutathione, which has been purified from a genetically modified A. fumigatus strain. The structures argue for stepwise processing of first the Phe and second the Ser moiety. Enzyme-mediated dehydration of the substrate activates GSH and a helix dipole stabilizes the resulting anion via a water molecule for the nucleophilic attack. Activity assays with mutants validate the interactions of GliG with the ligands and enrich our knowledge about enzymatic C-S bond formation in gliotoxin and epipolythiodioxopiperazine (ETP) natural compounds in general. | |||
Structural and mechanistic insights into C-S bond formation in gliotoxin.,Scherlach K, Kuttenlochner W, Scharf DH, Brakhage AA, Hertweck C, Groll M, Huber E Angew Chem Int Ed Engl. 2021 Apr 28. doi: 10.1002/anie.202104372. PMID:33909314<ref>PMID:33909314</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7nc3" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Aspfc]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Groll M]] | [[Category: Groll, M]] | ||
[[Category: Huber | [[Category: Huber, E M]] | ||
[[Category: Aspergillus fumigatus]] | |||
[[Category: Biosynthetic protein]] | |||
[[Category: Carbon-sulphur-bond]] | |||
[[Category: Epidithiodioxopiperazine]] | |||
[[Category: Glutathione-s-transferase]] | |||
[[Category: Mycotoxin]] | |||
Revision as of 18:00, 17 June 2021
Glutathione-S-transferase GliG (space group P212121)Glutathione-S-transferase GliG (space group P212121)
Structural highlights
Publication Abstract from PubMedGlutathione-S-transferases (GSTs) usually detoxify xenobiotics. The human pathogenic fungus Aspergillus fumigatus however uses the exceptional GST GliG to incorporate two sulphur atoms into its virulence factor gliotoxin. Because these sulphurs are essential for biological activity, glutathionylation is a key step of gliotoxin biosynthesis. Yet, the mechanism of carbon-sulphur linkage formation from a bis-hydroxylated precursor is unresolved. Here, we report structures of GliG with glutathione (GSH) and its reaction product cyclo[-l-Phe-l-Ser]-bis-glutathione, which has been purified from a genetically modified A. fumigatus strain. The structures argue for stepwise processing of first the Phe and second the Ser moiety. Enzyme-mediated dehydration of the substrate activates GSH and a helix dipole stabilizes the resulting anion via a water molecule for the nucleophilic attack. Activity assays with mutants validate the interactions of GliG with the ligands and enrich our knowledge about enzymatic C-S bond formation in gliotoxin and epipolythiodioxopiperazine (ETP) natural compounds in general. Structural and mechanistic insights into C-S bond formation in gliotoxin.,Scherlach K, Kuttenlochner W, Scharf DH, Brakhage AA, Hertweck C, Groll M, Huber E Angew Chem Int Ed Engl. 2021 Apr 28. doi: 10.1002/anie.202104372. PMID:33909314[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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