1dnc | pdb_00001dnc
HUMAN GLUTATHIONE REDUCTASE MODIFIED BY DIGLUTATHIONE-DINITROSO-IRON
|
Overview
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.
Disease
Known disease associated with this structure: Hemolytic anemia due to glutathione reductase deficiency OMIM:[138300]
About this Structure
1DNC is a Single protein structure of sequence from Homo sapiens with PO4, FAD and GTT as ligands. Active as Glutathione-disulfide reductase, with EC number 1.8.1.7 Full crystallographic information is available from OCA.
Reference
Enzyme inactivation through sulfhydryl oxidation by physiologic NO-carriers., Becker K, Savvides SN, Keese M, Schirmer RH, Karplus PA, Nat Struct Biol. 1998 Apr;5(4):267-71. PMID:9546215
Page seeded by OCA on Mon Nov 12 16:34:05 2007
