1DNC

HUMAN GLUTATHIONE REDUCTASE MODIFIED BY DIGLUTATHIONE-DINITROSO-IRON

1DNC の概要

• エントリーDOI: 10.2210/pdb1dnc/pdb
• 分子名称: GLUTATHIONE REDUCTASE, PHOSPHATE ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: sulfhydryl oxidation, sulfinic acid, nitric oxide, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform Mitochondrial: Mitochondrion. Isoform Cytoplasmic: Cytoplasm: P00390
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52856.09

構造登録者

Becker, K.,Savvides, S.N.,Keese, M.,Schirmer, R.H.,Karplus, P.A. (登録日: 1998-02-20, 公開日: 1998-05-27, 最終更新日: 2025-03-26)

主引用文献

Becker, K.,Savvides, S.N.,Keese, M.,Schirmer, R.H.,Karplus, P.A.
Enzyme inactivation through sulfhydryl oxidation by physiologic NO-carriers.
Nat.Struct.Biol., 5:267-271, 1998

PubMed Abstract: Nitric oxide (NO) is a pluripotent regulatory molecule, yet the molecular mechanisms by which it exerts its effects are largely unknown. Few physiologic target molecules of NO have been identified, and even for these, the modifications caused by NO remain uncharacterized. Human glutathione reductase (hGR), a central enzyme of cellular antioxidant defense, is inhibited by S-nitrosoglutathione (GSNO) and by diglutathionyl-dinitroso-iron (DNIC-[GSH]2), two in vivo transport forms of NO. Here, crystal structures of hGR inactivated by GSNO and DNIC-[GSH]2 at 1.7 A resolution provide the first picture of enzyme inactivation by NO-carriers: in GSNO-modified hGR, the active site residue Cys 63 is oxidized to an unusually stable cysteine sulfenic acid (R-SOH), whereas modification with DNIC-[GSH]2 oxidizes Cys 63 to a cysteine sulfinic acid (R-SO2H). Our results illustrate that various forms of NO can mediate distinct chemistry, and that sulfhydryl oxidation must be considered as a major mechanism of NO action.

PubMed: 9546215
DOI: 10.1038/nsb0498-267

実験手法

X-RAY DIFFRACTION (1.7 Å)