7nc6 | pdb_00007nc6

Glutathione-S-transferase GliG in complex with cyclo[L-Phe-L-Ser]-bis-glutathione-adduct

spinqualitylabelsall models 7nc6, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7nc6 is a 6 chain structure with sequence from Aspergillus fumigatus A1163. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: ACT, EDO, U8B Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B0Y813_ASPFC 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutathione S-transferase 3D structures

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