Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
Abstract

Thioredoxin (Trx) and glutathione (GSH) systems are considered to be two major redox systems in animal cells. They are reduced by NADPH via Trx reductase (TR) or oxidized GSH (GSSG) reductase and further supply electrons for deoxyribonucleotide synthesis, antioxidant defense, and redox regulation of signal transduction, transcription, cell growth, and apoptosis. We cloned and characterized a pyridine nucleotide disulfide oxidoreductase, Trx and GSSG reductase (TGR), that exhibits specificity for both redox systems. This enzyme contains a selenocysteine residue encoded by the TGA codon. TGR can reduce Trx, GSSG, and a GSH-linked disulfide in in vitro assays. This unusual substrate specificity is achieved by an evolutionary conserved fusion of the TR and glutaredoxin domains. These observations, together with the biochemical probing and molecular modeling of the TGR structure, suggest a mechanism whereby the C-terminal selenotetrapeptide serves a role of a protein-linked GSSG and shuttles electrons from the disulfide center within the TR domain to either the glutaredoxin domain or Trx.

Bibliography

Sun, Q.-A., Kirnarsky, L., Sherman, S., & Gladyshev, V. N. (2001). Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems. Proceedings of the National Academy of Sciences, 98(7), 3673–3678.

Authors 4
  1. Qi-An Sun (first)
  2. Leo Kirnarsky (additional)
  3. Simon Sherman (additional)
  4. Vadim N. Gladyshev (additional)
References 47 Referenced 234
  1. A Holmgren, E S J Arnér, F Åslund, M Björnstedt, L Zhong, J Ljung, H Nakamura, D Nikitovic Oxidative Stress, Cancer, AIDS, and Neurodegenerative Diseases, eds L Montagnier, R Olivier, C Pasquier (Dekker, New York), pp. 229–246 (1998). / Oxidative Stress, Cancer, AIDS, and Neurodegenerative Diseases by Holmgren A (1998)
  2. B Halliwell Free Radical Res 31, 261–272 (1999). (10.1080/10715769900300841) / Free Radical Res by Halliwell B (1999)
  3. H Sies Free Radical Biol Med 27, 916–921 (1999). (10.1016/S0891-5849(99)00177-X) / Free Radical Biol Med by Sies H (1999)
  4. S G Rhee Exp Mol Med 31, 53–59 (1999). (10.1038/emm.1999.9) / Exp Mol Med by Rhee S G (1999)
  5. T Finkel FEBS Lett 476, 52–54 (2000). (10.1016/S0014-5793(00)01669-0) / FEBS Lett by Finkel T (2000)
  6. J R Pedrajas, E Kosmidou, A Miranda-Vizuete, J A Gustafsson, A P Wright, G Spyrou J Biol Chem 274, 6366–6373 (1999). (10.1074/jbc.274.10.6366) / J Biol Chem by Pedrajas J R (1999)
  7. M S Seo, S W Kang, K Kim, I C Baines, T H Lee, S G Rhee J Biol Chem 275, 20346–20354 (2000). (10.1074/jbc.M001943200) / J Biol Chem by Seo M S (2000)
  8. R Brigelius-Flohe Free Radical Biol Med 27, 951–965 (1999). (10.1016/S0891-5849(99)00173-2) / Free Radical Biol Med by Brigelius-Flohe R (1999)
  9. D Mustacich, G Powis Biochem J 346, 1–8 (2000). (10.1042/bj3460001) / Biochem J by Mustacich D (2000)
  10. T C Stadtman Annu Rev Biochem 65, 83–100 (1996). (10.1146/annurev.bi.65.070196.000503) / Annu Rev Biochem by Stadtman T C (1996)
  11. V N Gladyshev, K-T Jeang, T C Stadtman Proc Natl Acad Sci USA 93, 6146–6151 (1996). (10.1073/pnas.93.12.6146) / Proc Natl Acad Sci USA by Gladyshev V N (1996)
  12. Q-A Sun, Y Wu, F Zappacosta, K T Jeang, B J Lee, D L Hatfield, V N Gladyshev J Biol Chem 274, 24522–24530 (1999). (10.1074/jbc.274.35.24522) / J Biol Chem by Sun Q-A (1999)
  13. E S J Arner, L Zhong, A Holmgren Methods Enzymol 300, 226–239 (1999). (10.1016/S0076-6879(99)00129-9) / Methods Enzymol by Arner E S J (1999)
  14. I K Smith, T L Vierheller, C A Thorne Anal Biochem 175, 408–413 (1988). (10.1016/0003-2697(88)90564-7) / Anal Biochem by Smith I K (1988)
  15. A Holmgren, F Aslund Methods Enzymol 252, 283–292 (1995). (10.1016/0076-6879(95)52031-7) / Methods Enzymol by Holmgren A (1995)
  16. F B Rudolph, H J Fromm Methods Enzymol 63, 138–159 (1979). (10.1016/0076-6879(79)63009-4) / Methods Enzymol by Rudolph F B (1979)
  17. J Ozols Methods Enzymol 182, 225–235 (1990). (10.1016/0076-6879(90)82019-X) / Methods Enzymol by Ozols J (1990)
  18. V N Gladyshev, V M Factor, F Housseau, D L Hatfield Biochem Biophys Res Commun 251, 488–493 (1998). (10.1006/bbrc.1998.9495) / Biochem Biophys Res Commun by Gladyshev V N (1998)
  19. S W Kessler Methods Enzymol 73, 442–459 (1981). (10.1016/0076-6879(81)73084-2) / Methods Enzymol by Kessler S W (1981)
  20. S Gromer, J Wissing, D Behne, K Ashman, R H Schirmer, L Flohe, K Becker Biochem J 332, 591–592 (1998). (10.1042/bj3320591) / Biochem J by Gromer S (1998)
  21. D Voet, J G Voet Biochemistry (Wiley, New York), pp. 541–548 (1995). / Biochemistry by Voet D (1995)
  22. P F Wang, L D Arscott, T W Gilberger, S Muller, C H Williams Biochemistry 38, 3187–3196 (1999). (10.1021/bi982674g) / Biochemistry by Wang P F (1999)
  23. L Zhong, E S Arner, A Holmgren Proc Natl Acad Sci USA 97, 5854–5859, . (First Published May 9, 2000; 10.1073/pnas.100114897). (2000). (10.1073/pnas.100114897) / Proc Natl Acad Sci USA by Zhong L (2000)
  24. M T Rodriguez-Manzaneque, J Ros, E Cabiscol, A Sorribas, E Herrero Mol Cell Biol 19, 8180–8190 (1999). (10.1128/MCB.19.12.8180) / Mol Cell Biol by Rodriguez-Manzaneque M T (1999)
  25. Y Wu, K S Kwon, S G Rhee FEBS Lett 440, 111–115 (1998). (10.1016/S0014-5793(98)01415-X) / FEBS Lett by Wu Y (1998)
  26. I Carlberg, B Mannervik Methods Enzymol 113, 484–490 (1985). (10.1016/S0076-6879(85)13062-4) / Methods Enzymol by Carlberg I (1985)
  27. C A Libreros-Minotta, J P Pardo, G Mendoza-Hernandez, J L Rendon Arch Biochem Biophys 298, 247–253 (1992). (10.1016/0003-9861(92)90119-H) / Arch Biochem Biophys by Libreros-Minotta C A (1992)
  28. B Mannervik, K Axelsson, K Larson Methods Enzymol 77, 281–285 (1981). (10.1016/S0076-6879(81)77038-1) / Methods Enzymol by Mannervik B (1981)
  29. J J Mieyal, D W Starke, S A Gravina, B A Hocevar Biochemistry 30, 8883–88891 (1991). (10.1021/bi00100a023) / Biochemistry by Mieyal J J (1991)
  30. M Luthman, A Holmgren J Biol Chem 257, 6686–6690 (1982). (10.1016/S0021-9258(18)34484-3) / J Biol Chem by Luthman M (1982)
  31. B Wieles, M van Agterveld, A Janson, J Clark-Curtiss, T Rinke de Wit, M Harboe, J Thole Mol Microbiol 16, 921–929 (1995). (10.1111/j.1365-2958.1995.tb02318.x) / Mol Microbiol by Wieles B (1995)
  32. J Kuriyan, T S Krishna, L Wong, B Guenther, A Pahler, C H Williams, P Model Nature (London) 352, 172–174 (1991). (10.1038/352172a0) / Nature (London) by Kuriyan J (1991)
  33. CH Williams FASEB J 9, 1267–1276 (1995). (10.1096/fasebj.9.13.7557016) / FASEB J by Williams CH (1995)
  34. L C Arscott, S Gromer, R H Schirmer, K Becker, C H Williams Proc Natl Acad Sci USA 94, 3621–3626 (1997). (10.1073/pnas.94.8.3621) / Proc Natl Acad Sci USA by Arscott L C (1997)
  35. P F Wang, J Marcinkeviciene, C H Williams, J S Blanchard Biochemistry 37, 16378–16389 (1998). (10.1021/bi980754e) / Biochemistry by Wang P F (1998)
  36. J R Gasdaska, J W Harney, P Y Gasdaska, G Powis, M J Berry J Biol Chem 274, 25379–25385 (1999). (10.1074/jbc.274.36.25379) / J Biol Chem by Gasdaska J R (1999)
  37. S R Lee, S Bar-Noy, J Kwon, R L Levine, T C Stadtman, S G Rhee Proc Natl Acad Sci USA 97, 2521–2526, . (First Published February 25, 2000; 10.1073/pnas.050579797). (2000). (10.1073/pnas.050579797) / Proc Natl Acad Sci USA by Lee S R (2000)
  38. L Zhong, A Holmgren J Biol Chem 275, 18121–18128 (2000). (10.1074/jbc.M000690200) / J Biol Chem by Zhong L (2000)
  39. B Rozell, A Holmgren, H A Hansson Eur J Cell Biol 46, 470–477 (1988). / Eur J Cell Biol by Rozell B (1988)
  40. P Y Gasdaska, M M Berggren, M J Berry, G Powis FEBS Lett 442, 105–111 (1999). (10.1016/S0014-5793(98)01638-X) / FEBS Lett by Gasdaska P Y (1999)
  41. S R Lee, J R Kim, K S Kwon, H W Yoon, R L Levine, A Ginsburg, S G Rhee J Biol Chem 274, 4722–4734 (1999). (10.1074/jbc.274.8.4722) / J Biol Chem by Lee S R (1999)
  42. A Miranda-Vizuete, A E Damdimopoulos, J R Pedrajas, J A Gustafsson, G Spyrou Eur J Biochem 261, 405–412 (1999). (10.1046/j.1432-1327.1999.00286.x) / Eur J Biochem by Miranda-Vizuete A (1999)
  43. S Watabe, Y Makino, K Ogawa, T Hiroi, Y Yamamoto, S Y Takahashi Eur J Biochem 264, 74–84 (1999). (10.1046/j.1432-1327.1999.00578.x) / Eur J Biochem by Watabe S (1999)
  44. M J Kelner, M A Montoya Biochem Biophys Res Commun 269, 366–368 (2000). (10.1006/bbrc.2000.2267) / Biochem Biophys Res Commun by Kelner M J (2000)
  45. L Zhao, A G Cox, J A Ruzicka, A A Bhat, W Zhang, E W Taylor Proc Natl Acad Sci USA 97, 6356–6361 (2000). (10.1073/pnas.97.12.6356) / Proc Natl Acad Sci USA by Zhao L (2000)
  46. N Schiering, W Kabsch, M J Moore, M D Distefano, C T Walsh, E F Pai Nature (London) 352, 168–172 (1991). (10.1038/352168a0) / Nature (London) by Schiering N (1991)
  47. S Engst, S M Miller Biochemistry 38, 3519–3529 (1999). (10.1021/bi982680c) / Biochemistry by Engst S (1999)
Dates
Type When
Created 23 years, 1 month ago (July 26, 2002, 10:44 a.m.)
Deposited 3 years, 3 months ago (June 7, 2022, 1:43 a.m.)
Indexed 2 weeks, 4 days ago (Aug. 19, 2025, 6:19 a.m.)
Issued 24 years, 5 months ago (March 20, 2001)
Published 24 years, 5 months ago (March 20, 2001)
Published Online 24 years, 5 months ago (March 20, 2001)
Published Print 24 years, 5 months ago (March 27, 2001)
Funders 0

None

@article{Sun_2001, title={Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.051454398}, DOI={10.1073/pnas.051454398}, number={7}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Sun, Qi-An and Kirnarsky, Leo and Sherman, Simon and Gladyshev, Vadim N.}, year={2001}, month=mar, pages={3673–3678} }