title: Structural basis for target protein recognition by the protein disulfide reductase thioredoxin.
abstract: Thioredoxin is ubiquitous and regulates various target proteins through disulfide bond reduction. We report the structure of thioredoxin (HvTrxh2 from barley) in a reaction intermediate complex with a protein substrate, barley alpha-amylase/subtilisin inhibitor (BASI). The crystal structure of this mixed disulfide shows a conserved hydrophobic motif in thioredoxin interacting with a sequence of residues from BASI through van der Waals contacts and backbone-backbone hydrogen bonds. The observed structural complementarity suggests that the recognition of features around protein disulfides plays a major role in the specificity and protein disulfide reductase activity of thioredoxin. This novel insight into the function of thioredoxin constitutes a basis for comprehensive understanding of its biological role. Moreover, comparison with structurally related proteins shows that thioredoxin shares a mechanism with glutaredoxin and glutathione transferase for correctly positioning substrate cysteine residues at the catalytic groups but possesses a unique structural element that allows recognition of protein disulfides.
authors.affiliation: Enzyme and Protein Chemistry, BioCentrum-DTU, Søltofts Plads, Building 224, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Kenji
authors.initials: K
authors.lastname: Maeda
authors.forename: Per
authors.initials: P
authors.lastname: Hägglund
authors.forename: Christine
authors.initials: C
authors.lastname: Finnie
authors.forename: Birte
authors.initials: B
authors.lastname: Svensson
authors.forename: Anette
authors.initials: A
authors.lastname: Henriksen
mesh_terms: D020816:Amino Acid Motifs; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D054477:Glutaredoxins; D005978:Glutathione / Q000737:chemistry; D005982:Glutathione Transferase / Q000737:chemistry / Q000378:metabolism; D001467:Hordeum; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010088:Oxidoreductases / Q000737:chemistry; D011490:Protein Disulfide Reductase (Glutathione) / Q000737:chemistry*; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry; D013879:Thioredoxins / Q000737:chemistry*
chemical_list: D004220:Disulfides; D054477:Glutaredoxins; D011506:Proteins; D013879:Thioredoxins; D010088:Oxidoreductases; D011490:Protein Disulfide Reductase (Glutathione); D005982:Glutathione Transferase; D005978:Glutathione; D003545:Cysteine