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Mammalian thioredoxin reductase: Oxidation of the C-terminal cysteine/selenocysteine active site forms a thioselenide, and replacement of selenium with sulfur markedly reduces catalytic activity
Open accessAbstract
Mammalian cytosolic thioredoxin reductase (TrxR) has a redox center, consisting of Cys 59 /Cys 64 adjacent to the flavin ring of FAD and another center consisting of Cys 497 /selenocysteine (SeCys) 498 near the C terminus. We now show that the C-terminal Cys 497 -SH/SeCys 498 -Se − of NADPH-reduced enzyme, after anaerobic dialysis, was converted to a thioselenide on incubation with excess oxidized Trx (TrxS 2 ) or H 2 O 2 . The Cys 59 -SH/Cys 64 -SH pair also was oxidized to a disulfide. At lower concentrations of TrxS 2 , the Cys 59 -SH/Cys 64 -SH center was still converted to a disulfide, presumably by reduction of the thioselenide to Cys 497 -SH/SeCys 498 -Se − . Specific alkylation of SeCys 498 completely blocked the TrxS 2 -induced oxidation of Cys 59 -SH/Cys 64 -SH, and the alkylated enzyme had negligible NADPH-disulfide oxidoreductase activity. The effect of replacing SeCys 498 with Cys was determined by using a mutant form of human placental TrxR1 expressed in Escherichia coli . The NADPH-disulfide oxidoreductase activity of the purified Cys 497 /Cys 498 mutant enzyme was 6% or 11% of that of wild-type rat liver TrxR1 with 5,5′-dithio bis (2-nitrobenzoic acid) or TrxS 2 , respectively, as substrate. Disulfide formation induced by excess TrxS 2 in the mutant form was 12% of that of the wild type. Thus, SeCys has a critical redox function during the catalytic cycle, which is performed poorly by Cys.
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Principles of Protein Structure
Schulz, G. E., & Schirmer, R. H. (1979) · Springer Advanced Texts in Chemistry · doi:10.1007/978-1-4612-6137-7 · Cited by 1,105
Principles of protein structure
(1980) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(80)90019-9 · Cited by 1,058
Thioredoxin-dependent peroxide reductase from yeast.
Chae, H. Z., Chung, S. J., & Rhee, S. G. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47038-x · Cited by 957
Self-citationRat liver thioredoxin and thioredoxin reductase: purification and characterization
Luthman, M., & Holmgren, A. (1982) · Biochemistry · doi:10.1021/bi00269a003 · Cited by 602
Tamura, T., & Stadtman, T. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.3.1006 · Cited by 539
Self-citationGladyshev, V. N., Jeang, K. T., & Stadtman, T. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.6146 · Cited by 468
Self-citationApffel, A., Fischer, S., Goldberg, G., Goodley, P. C., & Kuhlmann, F. E. (1995) · Journal of Chromatography A · doi:10.1016/0021-9673(95)00175-m · Cited by 344
Redox Regulation of Cell Signaling by Selenocysteine in Mammalian Thioredoxin Reductases
Sun, Q.-A., Wu, Y., Zappacosta, F., Jeang, K.-T., Lee, B. J., Hatfield, D. L., & Gladyshev, V. N. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.35.24522 · Cited by 323
Lee, S.-R., Kim, J.-R., Kwon, K.-S., Yoon, H. W., Levine, R. L., Ginsburg, A., & Rhee, S. G. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.8.4722 · Cited by 274
Self-citationZhong, L., Arnér, E. S. J., Ljung, J., Åslund, F., & Holmgren, A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.15.8581 · Cited by 263
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Schafer, F. Q., & Buettner, G. R. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00480-4 · Cited by 4,587
Nordberg, J., & Arnér, E. S. J. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00724-9 · Cited by 2,662
Lubos, E., Loscalzo, J., & Handy, D. E. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3586 · Cited by 1,280
Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals
Moskovitz, J., Bar-Noy, S., Williams, W. M., Requena, J., Berlett, B. S., & Stadtman, E. R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.231472998 · Cited by 677
Self-citationFocus on mammalian thioredoxin reductases — Important selenoproteins with versatile functions
Arnér, E. S. J. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.01.014 · Cited by 673
Metadata
- Authors
- Lee, S.-R., Bar-Noy, S., Kwon, J., Levine, R. L., Stadtman, T. C., & Rhee, S. G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2000-02-25
- Volume
- 97
- Issue
- 6
- Pages
- 2521-2526
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1970416169
- Cited by
- 269
- References
- 18
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- green
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- Lee, S.-R., Bar-Noy, S., Kwon, J., Levine, R. L., Stadtman, T. C., & Rhee, S. G. (2000). Mammalian thioredoxin reductase: Oxidation of the C-terminal cysteine/selenocysteine active site forms a thioselenide, and replacement of selenium with sulfur markedly reduces catalytic activity. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.050579797
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