Biochemistry, Department of


Date of this Version

June 2006


Published in Selenium: Its molecular biology and role in human health, Second Edition, edited by Dolph L. Hatfield, Marla J. Berry, and Vadim N. Gladyshev. Springer Science+Business Media LLC, 2006. Pages 123–133. Copyright © 2006 Springer Science+Business Media LLC. Used by permission.


Methionine residues in proteins can be readily oxidized to a diastereomeric mixture of methionine sulfoxides by reactive oxygen species. In most organisms, methionine sulfoxides are reversibly and stereospecifically reduced back to methionine by two distinct classes of repair enzymes, methionine-S-sulfoxide reductase (MsrA) and methionine-R-sulfoxide reductase (MsrB). Methionine sulfoxide reduction is thought to be an essential pathway that protects cells from oxidative stress and regulates protein function. This pathway is also implicated in delaying the aging process in organisms from yeast to mammals. The first selenoprotein identified using bioinformatics methods, SelR (also known as SelX or MsrB1), was recently found to be a selenocysteine-containing MsrB. In mammals, selenoprotein MsrB1 is a major MsrB, while MsrB2 and MsrB3 contain cysteine in place of selenocysteine. It has been found that selenocysteine- and cysteine-containing MsrBs employ different catalytic mechanisms. Interestingly, a selenocysteine-containing form of MsrA was also described, but so far was only detected in green algae.