title: Crystal structure of fully oxidized human thioredoxin.
abstract: In addition to the active cysteines located at positions 32 and 35 in humans, mammalian cytosolic thioredoxin (TRX) possesses additional conserved cysteine residues at positions 62, 69, and 73. These non-canonical cysteine residues, that are distinct from prokaryotic TRX and also not found in mammalian mitochondrial TRX, have been implicated in biological functions regulating signal transduction pathways via their post-translational modifications. Here, we describe for the first time the structure of a fully oxidized TRX. The structure shows a non-active Cys62-Cys69 disulfide bond in addition to the active Cys32-Cys35 disulfide. The non-active disulfide switches the α3-helix of TRX, composed of residues Cys62 to Glu70, to a bulging loop and dramatically changes the environment of the TRX residues involved in the interaction with its reductase and other cellular substrates. This structural modification may have implications for a number of potential functions of TRX including the regulation of redox-dependent signaling pathways.
authors.affiliation: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea.
authors.forename: Jungwon
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea; Department of Biochemistry, Chungnam National University, Daejeon 34134, South Korea.
authors.forename: Loi T
authors.initials: LT
authors.lastname: Nguyen
authors.affiliation: College of Pharmacy, Korea University, Sejong 30019, South Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Jeon
authors.affiliation: Department of Biochemistry, Chungnam National University, Daejeon 34134, South Korea.
authors.forename: Chan Yong
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea. Electronic address: mhk8n@kribb.re.kr.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Kim
mesh_terms: D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008958:Models, Molecular; D010084:Oxidation-Reduction; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D013879:Thioredoxins / Q000737:chemistry* / Q000235:genetics
chemical_list: D004220:Disulfides; D011994:Recombinant Proteins; C491203:TXN protein, human; D013879:Thioredoxins; D003545:Cysteine
keywords: Oxidoreductase; Redox; Thioredoxin; X-ray structure