Catalytic advantages provided by selenocysteine in methionine-S-sulfoxide reductases

Hwa Young Kim, Dmitri Fomenko, Yeo Eun Yoon, Vadim N. Gladyshev

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Methionine sulfoxide reductases are key enzymes that repair oxidatively damaged proteins. Two distinct stereospecific enzyme families are responsible for this function: MsrA (methionine-5-sulfoxide reductase) and MsrB (methionine-R-sulfoxide reductase). In the present study, we identified multiple selenoprotein MsrA sequences in organisms from bacteria to animals. We characterized the selenocysteine (Sec)-containing Chlamydomonas MsrA and found that this protein exhibited 10-50-fold higher activity than either its cysteine (Cys) mutant form or the natural mouse Cys-containing MsrA, making this selenoenzyme the most efficient MsrA known. We also generated a selenoprotein form of mouse MsrA and found that the presence of Sec increased the activity of this enzyme when a resolving Cys was mutated in the protein. These data suggest that the presence of Sec improves the reduction of methionine sulfoxide by MsrAs. However, the oxidized selenoprotein could not always be efficiently reduced to regenerate the active enzyme. Overall, this study demonstrates that sporadically evolved Sec-containing forms of methionine sulfoxide reductases reflect catalytic advantages provided by Sec in these and likely other thiol-dependent oxidoreductases.

Original languageEnglish (US)
Pages (from-to)13697-13704
Number of pages8
JournalBiochemistry
Volume45
Issue number46
DOIs
StatePublished - Nov 21 2006

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Methionine Sulfoxide Reductases
Selenocysteine
Methionine
Selenoproteins
Cysteine
Enzymes
Chlamydomonas
Proteins
Sulfhydryl Compounds
sulfoxide reductase
methionine sulfoxide reductase
Bacteria
Oxidoreductases
Animals
Repair

ASJC Scopus subject areas

  • Biochemistry

Cite this

Catalytic advantages provided by selenocysteine in methionine-S-sulfoxide reductases. / Kim, Hwa Young; Fomenko, Dmitri; Yoon, Yeo Eun; Gladyshev, Vadim N.

In: Biochemistry, Vol. 45, No. 46, 21.11.2006, p. 13697-13704.

Research output: Contribution to journalArticle

Kim, Hwa Young ; Fomenko, Dmitri ; Yoon, Yeo Eun ; Gladyshev, Vadim N. / Catalytic advantages provided by selenocysteine in methionine-S-sulfoxide reductases. In: Biochemistry. 2006 ; Vol. 45, No. 46. pp. 13697-13704.
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