1GSN

HUMAN GLUTATHIONE REDUCTASE MODIFIED BY DINITROSOGLUTATHIONE

Summary for 1GSN

• Entry DOI: 10.2210/pdb1gsn/pdb
• Descriptor: GLUTATHIONE REDUCTASE, PHOSPHATE ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• Functional Keywords: sulfhydryl oxidation, sulfenic acid, nitric oxide, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Isoform Mitochondrial: Mitochondrion. Isoform Cytoplasmic: Cytoplasm: P00390
• Total number of polymer chains: 1
• Total formula weight: 52888.09

Authors

Becker, K.,Savvides, S.N.,Keese, M.,Schirmer, R.H.,Karplus, P.A. (deposition date: 1998-02-21, release date: 1998-05-27, Last modification date: 2011-12-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.7 Å)