Functions and Evolution of Selenoprotein Methionine Sulfoxide Reductases

Authors

Byung Cheon Lee, University of Nebraska-Lincoln
Alexander Dikiy, Norwegian University of Science and Technology
Hwa-Young Kim, Aging-associated Vascular Disease Research Center, Yeungnam University College of Medicine, Daegu 705-717, Republic of KoreaFollow
Vadim N. Gladyshev, University of Nebraska-LincolnFollow

Date of this Version

2009

Comments

Published in Biochimica et Biophysica Acta (BBA)—General Subjects (2009); doi 10.1016/j.bbagen.2009.04.014 Copyright © 2009 Elsevier B.V. Used by permission. http://www.elsevier.com/locate/bbagen

Abstract

Methionine sulfoxide reductases (Msrs) are thiol-dependent enzymes which catalyze conversion of methionine sulfoxide to methionine. Three Msr families, MsrA, MsrB, and fRMsr, are known. MsrA and MsrB are responsible for the reduction of methionine-S-sulfoxide and methionine-R-sulfoxide residues in proteins, respectively, whereas fRMsr reduces free methionine-R-sulfoxide. Besides acting on proteins, MsrA can addi¬tionally reduce free methionine-S-sulfoxide. Some MsrAs and MsrBs evolved to utilize catalytic selenocysteine. This includes MsrB1, which is a major MsrB in cytosol and nucleus in mammalian cells. Specialized machinery is used for insertion of selenocysteine into MsrB1 and other seleno¬proteins at in-frame UGA codons. Selenocysteine offers catalytic advantage to the protein repair function of Msrs, but also makes these proteins dependent on the supply of selenium and requires adjustments in their strategies for regeneration of active enzymes. Msrs have roles in protecting cellular proteins from oxidative stress and through this function they may regulate lifespan in several model organisms.