title: Structural and functional diversity of glutaredoxins in yeast.
abstract: Glutaredoxins are defined as thiol disulfide oxidoreductases that reduce disulfide bonds employing reduced glutathione as electron donor. They constitute a complex family of proteins with a diversity of enzymatic and functional properties. Thus, dithiol glutaredoxins are able to reduce disulfide bonds and deglutathionylate mixed disulfides between glutathione and cysteine protein residues. They could act regulating the redox state of sulfhydryl residues of specific proteins, while thioredoxins (another family of thiol disulfide oxidoreductases which employ NADPH as electron donor) would be the general sulfhydryl reductants. Some dithiol glutaredoxins such as human Grx2 form dimers bridged by one iron-sulfur cluster, which acts as a sensor of oxidative stress, therefore regulating the activity of the glutaredoxin. The ability to interact with iron-sulfur clusters as ligands is also characteristic of monothiol glutaredoxins with a CGFS-type active site. These do not display thiol oxidoreductase activity, but have roles in iron homeostasis. The three members of this subfamily in Saccharomyces cerevisiae participate in the synthesis of the iron-sulfur clusters in mitochondria (Grx5), or in signalling the iron status inside the cell for regulation of iron uptake and intracellular iron relocalization (Grx3 and Grx4). Such a role in iron metabolism seems to be evolutionary conserved. Fungal cells also contain membrane-associated glutaredoxins structurally and enzymatically similar to dithiol glutaredoxins, which may act as redox regulators at the early stages of the protein secretory machinery.
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, IRBLleida, Universitat de Lleida, Montserrat Roig 2, 25008-Lleida, Spain. enric.herrero@cmb.udl.cat
authors.forename: Enrique
authors.initials: E
authors.lastname: Herrero
authors.forename: Gemma
authors.initials: G
authors.lastname: Bellí
authors.forename: Celia
authors.initials: C
authors.lastname: Casa
mesh_terms: D054477:Glutaredoxins / Q000737:chemistry* / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000378:metabolism*
chemical_list: D054477:Glutaredoxins; D011506:Proteins; D007501:Iron