| Structural highlights
Function
THIO_HUMAN Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity.[1] [2] [3] [4] [5] ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).[6] [7] [8] [9] [10]
Publication Abstract from PubMed
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 alpha3-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.
Crystal structure of fully oxidized human thioredoxin.,Hwang J, Nguyen LT, Jeon YH, Lee CY, Kim MH Biochem Biophys Res Commun. 2015 Nov 13;467(2):218-22. doi:, 10.1016/j.bbrc.2015.10.003. Epub 2015 Oct 9. PMID:26453009[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jacquot JP, de Lamotte F, Fontecave M, Schurmann P, Decottignies P, Miginiac-Maslow M, Wollman E. Human thioredoxin reactivity-structure/function relationship. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1375-81. PMID:2176490
- ↑ Hirota K, Matsui M, Iwata S, Nishiyama A, Mori K, Yodoi J. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-8. PMID:9108029
- ↑ Wei SJ, Botero A, Hirota K, Bradbury CM, Markovina S, Laszlo A, Spitz DR, Goswami PC, Yodoi J, Gius D. Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation. Cancer Res. 2000 Dec 1;60(23):6688-95. PMID:11118054
- ↑ Mitchell DA, Marletta MA. Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine. Nat Chem Biol. 2005 Aug;1(3):154-8. Epub 2005 Jul 10. PMID:16408020 doi:http://dx.doi.org/nchembio720
- ↑ Mitchell DA, Morton SU, Fernhoff NB, Marletta MA. Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11609-14. Epub 2007 Jul 2. PMID:17606900 doi:http://dx.doi.org/0704898104
- ↑ Jacquot JP, de Lamotte F, Fontecave M, Schurmann P, Decottignies P, Miginiac-Maslow M, Wollman E. Human thioredoxin reactivity-structure/function relationship. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1375-81. PMID:2176490
- ↑ Hirota K, Matsui M, Iwata S, Nishiyama A, Mori K, Yodoi J. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-8. PMID:9108029
- ↑ Wei SJ, Botero A, Hirota K, Bradbury CM, Markovina S, Laszlo A, Spitz DR, Goswami PC, Yodoi J, Gius D. Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation. Cancer Res. 2000 Dec 1;60(23):6688-95. PMID:11118054
- ↑ Mitchell DA, Marletta MA. Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine. Nat Chem Biol. 2005 Aug;1(3):154-8. Epub 2005 Jul 10. PMID:16408020 doi:http://dx.doi.org/nchembio720
- ↑ Mitchell DA, Morton SU, Fernhoff NB, Marletta MA. Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11609-14. Epub 2007 Jul 2. PMID:17606900 doi:http://dx.doi.org/0704898104
- ↑ Hwang J, Nguyen LT, Jeon YH, Lee CY, Kim MH. Crystal structure of fully oxidized human thioredoxin. Biochem Biophys Res Commun. 2015 Nov 13;467(2):218-22. doi:, 10.1016/j.bbrc.2015.10.003. Epub 2015 Oct 9. PMID:26453009 doi:http://dx.doi.org/10.1016/j.bbrc.2015.10.003
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