| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BACKGROUND: Thioredoxin is a ubiquitous protein and is involved in a variety of fundamental biological functions. Its active site is conserved and has two redox active cysteines in the sequence Trp-Cys-Gly-Pro-Cys. No structures of the oxidized and reduced states from the same species have been determined at high resolution under the same conditions and using the same methods. Hence, any detailed comparison of the two oxidation states has been previously precluded. RESULTS: The reduced and oxidized states of the (C62A, C69A, C73A) mutant of human thioredoxin have been investigated by multidimensional heteronuclear NMR. Structures for both states were determined on the basis of approximately 28 experimental restraints per residue, and the resulting precision of the two structures is very high. Consequently, subtle differences between the oxidized and reduced states can be reliably assessed and evaluated. Small differences, particularly within and around the active site can be discerned. CONCLUSIONS: Overall, the structures of the reduced and oxidized states of the (C62A, C69A, C73A) mutant of human thioredoxin are very similar (with a backbone atomic root mean square difference of about 0.9 A) and the packing of side chains within the protein core is nearly identical. The conformational change between oxidized and reduced human thioredoxin is very small and localized to areas in spatial proximity to the redox active cysteines. These subtle structural differences, in addition to the restriction of conformational freedom within the active site upon oxidation, may be important for the different activities of thioredoxin involving a variety of target proteins.
The high-resolution three-dimensional solution structures of the oxidized and reduced states of human thioredoxin.,Qin J, Clore GM, Gronenborn AM Structure. 1994 Jun 15;2(6):503-22. PMID:7922028[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
- ↑ Qin J, Clore GM, Gronenborn AM. The high-resolution three-dimensional solution structures of the oxidized and reduced states of human thioredoxin. Structure. 1994 Jun 15;2(6):503-22. PMID:7922028
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