Inhibition of methionine sulfoxide reduction by dimethyl sulfoxide.
Dimethyl sulfoxide (DMSO) is widely used in chemistry and biology as a solvent and as a cryoprotectant. It is also used as a pharmaceutical agent for the treatment of interstitial cystitis and rheumatoid arthritis. Previous reports described DMSO as being reduced by methionine-S-sulfoxide reductase (MsrA). However, little is known about the DMSO reduction capability of methionine-R-sulfoxide reductase (MsrB) or its effect on the catalysis of methionine sulfoxide reduction. We show that mammalian MsrB2 and MsrB3 were unable to reduce DMSO. This compound inhibited MsrB2 activity but did not inhibit MsrB3 activity. We further determined that DMSO functions as an inhibitor of MsrA and MsrB2 in the reduction of methionine sulfoxides via different inhibition mechanisms. DMSO competitively inhibited MsrA activity but acted as a non-competitive inhibitor of MsrB2 activity. Our study also demonstrated that DMSO inhibits in vivo methionine sulfoxide reduction in yeast and mammalian cells. [BMB reports 2009; 42(9): 580-585].
Kwak
Geun-Hee
GH
Department of Biochemistry and Molecular Biology, Aging-associated Vascular Disease Research Center, Yeungnam University College of Medicine, Daegu, Korea.
Choi
Seung Hee
SH
Kim
Jae-Ryong
JR
Kim
Hwa-Young
HY
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008715:Methionine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development
D016166:Free Radical Scavengers; D009249:NADP; D008715:Methionine; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; D051150:Methionine Sulfoxide Reductases; C487504:MsrA protein, S cerevisiae; C027219:methionine sulfoxide reductase; C524352:MSRB3 protein, human; C013111:methionine sulfoxide; D004121:Dimethyl Sulfoxide