Volume 85 Issue 35 | p. 14 | News of The Week
Issue Date: August 27, 2007

Selenium Doubles Up In Proteins

Diselenide bonds could play a role in redox regulation
Department: Science & Technology
News Channels: Biological SCENE

THE FIRST REPORT of a selenium-selenium bond in naturally occurring proteins characterizes the linkage's low redox potential and suggests that it might play a role in regulation of redox levels in cells (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0703448104).

The bond, described by a team led by biochemist Vadim Gladyshev at the University of Nebraska, unites two nearby selenocysteine residues in members of a protein family found mainly in aquatic animals and bacteria. Mass spectrometry sequencing verified the selenium-selenium bond and revealed a characteristic isotope signature of a compound containing two selenium atoms.

The two linked selenocysteines are located in these proteins' active site and are organized in a manner reminiscent of the pair of catalytic cysteines found in the active site of thioredoxins. These proteins use a reversible disulfide bond to reduce cellular substrates. On the basis of this similarity, Gladyshev suggests that the new protein family may play a similar role in redox regulation.

The diselenide bond doesn't react with small-molecule reducing agents, indicating that it has a very low redox potential. A team led by Phil Dawson, a protein chemist at Scripps Research Institute, reported last year that a synthetic protein with an engineered diselenide bond can be partially reduced by thioredoxin. This represents a potential avenue for reduction of diselenide bonds in a catalytic cycle.

"Many people had suggested that these linkages were too oxidatively stable to be useful under physiological conditions," Dawson says. The identification of a naturally occurring diselenide bond, however, suggests that nature can harness its low redox potential.

Other known selenocysteine-containing proteins tend to also have a naked cysteine residue, and the two amino acids form a reversible selenium-sulfur bond.

It isn't yet clear why diselenide-containing proteins overwhelmingly occur in aquatic organisms and what mechanisms exist for reducing the diselenide bond in vivo, but the nature of this linkage suggests a role for these proteins in cellular redox regulation.

 
Chemical & Engineering News
ISSN 0009-2347
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