title: Solution structure of Escherichia coli glutaredoxin-2 shows similarity to mammalian glutathione-S-transferases.
abstract: Glutaredoxin 2 (Grx2) from Escherichia coli is distinguished from other glutaredoxins by its larger size, low overall sequence identity and lack of electron donor activity with ribonucleotide reductase. However, catalysis of glutathione (GSH)-dependent general disulfide reduction by Grx2 is extremely efficient. The high-resolution solution structure of E. coli Grx2 shows a two-domain protein, with residues 1 to 72 forming a classical "thioredoxin-fold" glutaredoxin domain, connected by an 11 residue linker to the highly helical C-terminal domain, residues 84 to 215. The active site, Cys9-Pro10-Tyr11-Cys12, is buried in the interface between the two domains, but Cys9 is solvent-accessible, consistent with its role in catalysis. The structures reveal the hither to unknown fact that Grx2 is structurally similar to glutathione-S-transferases (GST), although there is no obvious sequence homology. The similarity of these structures gives important insights into the functional significance of a new class of mammalian GST-like proteins, the single-cysteine omega class, which have glutaredoxin oxidoreductase activity rather than GSH-S-transferase conjugating activity. E. coli Grx 2 is structurally and functionally a member of this new expanding family of large glutaredoxins. The primary function of Grx2 as a GST-like glutaredoxin is to catalyze reversible glutathionylation of proteins with GSH in cellular redox regulation including stress responses.
authors.affiliation: Department of Molecular Biology and Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: B
authors.initials: B
authors.lastname: Xia
authors.forename: A
authors.initials: A
authors.lastname: Vlamis-Gardikas
authors.forename: A
authors.initials: A
authors.lastname: Holmgren
authors.forename: P E
authors.initials: PE
authors.lastname: Wright
authors.forename: H J
authors.initials: HJ
authors.lastname: Dyson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003545:Cysteine / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D019143:Evolution, Molecular; D054477:Glutaredoxins; D005982:Glutathione Transferase / Q000737:chemistry* / Q000145:classification; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D010088:Oxidoreductases; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D012996:Solutions
chemical_list: D004220:Disulfides; C516005:GLRX protein, human; C516008:GLRX2 protein, human; D054477:Glutaredoxins; D011506:Proteins; D012996:Solutions; D010088:Oxidoreductases; D005982:Glutathione Transferase; D003545:Cysteine