Abstract
Mammalian thioredoxin reductases (Trx Rs) contain selenium as selenocysteine (Sec) in the C-terminal redox center-Gly-Cys-Sec-Gly-OH to reduce Trx and other substrates; a Sec-to-Cys substitution in mammalian TrxR yields an almost inactive enzyme. The corresponding tetrapeptide sequence in Drosophila melanogaster TrxR (Dm-TrxR),-Ser-Cys-Cys-Ser-OH, endows the orthologous enzyme with a catalytic competence similar to mammalian selenoenzymes, but implementation of the Ser-containing tetrapeptide sequence SCCS into the mammalian enzyme does not restore the activity of the Sec-to-Cys mutant form (turnover number <2/min). MOPAC calculation suggested that the C-terminal hexapeptide Pro-Ala-Ser-Cys-Cys-Ser-OH functions as a redox center that alleviates the necessity for selenium in Dm-TrxR, and a mutant form of human lung TrxR that mimics this hexapeptide sequence showed improved catalytic turnover (17.4/min for DTNB and 13.2/min for E. coli trx) compared to the Sec-to-Cys mutant. MOPAC calculation also suggested that the dominant form of the Procontaining hexapeptide is a C+ conformation, which perhaps has a catalytic advantage in facile reduction of the intramolecular disulfide bond between Cys497 and Cys498 by the N-terminal redox center in the neighboring subunit.
Original language | English |
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Pages (from-to) | 516-521 |
Number of pages | 6 |
Journal | Bioscience, Biotechnology and Biochemistry |
Volume | 75 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2011 |
Keywords
- Drosophila melanogaster
- Redox motif
- Selenocysteine
- Semiempirical molecular orbital calculation
- Thioredoxin reductase
ASJC Scopus subject areas
- Biotechnology
- Analytical Chemistry
- Biochemistry
- Applied Microbiology and Biotechnology
- Molecular Biology
- Organic Chemistry