Roles of methionine suldfoxide reductases in antioxidant defense, protein regulation and survival.
One of the most oxidation-sensitive amino acids is methionine. Oxidation of methionine to methionine sulfoxide (MetO) could, on the one hand, be an important component of signal transduction pathways and on the other hand, may lower the cellular antioxidant capacity, alter protein function, interfere with signal transduction, and damage proteins. The latter changes could lead to the accumulation and malfunction of various proteins. As a result, enhanced development of certain diseases and signs of aging may occur. So far, two major enzymes that could reduce MetO in proteins have been described, denoted as MsrA and MsrB (Methionine sulfoxide reductases). In general, Msrs have been shown to be important in protecting cells from oxidative stress throughout many species from bacteria to mammals. In addition, the activities of certain enzymes could be restored or controlled following reduction of their MetO residues, through the Msr system. Of all Msrs, MsrA seems to be important in controlling MetO reduction in general and MsrB, thioredoxin reductase (Trr), and the adhesion capabilities of certain bacterial cells in particular. The recently discovered MsrB can reduce specifically the R-MetO enantiomer while MsrA can reduce specifically the S-MetO enantiomer. Another significant difference between MsrA and MsrB is that the latter's major form in mammalian cells is a selenoprotein. The current review will discuss the major characteristics of methionine sulfoxide reductases as physiological antioxidants, repair systems, and cellular regulating enzymes.
Moskovitz
Jackob
J
The University of Kansas, Department of Pharmacology and Toxicology, School of Pharmacy, Lawrence, KS 66045-7582, USA. moskovij@ku.edu
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives* / Q000378:metabolism*; D051150:Methionine Sulfoxide Reductases; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051140:Selenoproteins
D000975:Antioxidants; D011506:Proteins; D051140:Selenoproteins; D008715:Methionine; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; C013111:methionine sulfoxide