7NCB

Glutathione-S-transferase GliG mutant H26A

7NCB の概要

• エントリーDOI: 10.2210/pdb7ncb/pdb
• 関連するPDBエントリー: 7NC3
• 分子名称: Glutathione S-transferase GliG (2 entities in total)
• 機能のキーワード: aspergillus fumigatus, mycotoxin, glutathione-s-transferase, carbon-sulphur-bond, epidithiodioxopiperazine, biosynthetic protein
• 由来する生物種: Neosartorya fumigata (strain CEA10 / CBS 144.89 / FGSC A1163)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57791.89

構造登録者

Groll, M.,Huber, E.M. (登録日: 2021-01-28, 公開日: 2021-05-12, 最終更新日: 2024-01-31)

主引用文献

Scherlach, K.,Kuttenlochner, W.,Scharf, D.H.,Brakhage, A.A.,Hertweck, C.,Groll, M.,Huber, E.M.
Structural and Mechanistic Insights into C-S Bond Formation in Gliotoxin.
Angew.Chem.Int.Ed.Engl., 60:14188-14194, 2021

PubMed Abstract: Glutathione-S-transferases (GSTs) usually detoxify xenobiotics. The human pathogenic fungus Aspergillus fumigatus however uses the exceptional GST GliG to incorporate two sulfur atoms into its virulence factor gliotoxin. Because these sulfurs are essential for biological activity, glutathionylation is a key step of gliotoxin biosynthesis. Yet, the mechanism of carbon-sulfur 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.

PubMed: 33909314
DOI: 10.1002/anie.202104372

実験手法

X-RAY DIFFRACTION (1.85 Å)