One of the known post-translational modification of proteins is the oxidation of methionine residues to methionine sulfoxide [Met(O)]. This oxidation can readily occur since a variety of reactive molecules, which are by-products of aerobic metabolism, are capable of causing this oxidation (i.e. superoxide anion, hydrogen peroxide, hydroxyl radical, and hypochlorite ion). It is of interest that this oxidation is reversible. An enzyme, peptide methionine sulfoxide reductase (MsrA), which has been detected in virtually all organisms examined, catalyzes the reduction of methionine sulfoxide residues in proteins to methionine. Recently, it has been shown that the recombinant MsrA from Escherichia coli and the cow can reduce methyl sulfoxide compounds including free methionine sulfoxide. Also, it has been shown that the enzyme has been found in the medulla of the kidney, cerebellar neurons, peritoneal macrophages, and the retina. In the present study, we cloned the human gene and localized it to chromosome 8p23. This locus has """"""""hot spots"""""""" for mutations /deletions that can cause cancer and retinitis pigmentosa. Experiments are underway to determine whether msrA gene is involved in these diseases. Also, the msrA gene from yeast has been cloned and expressed, and a """"""""knock-out"""""""" experiment is in progress to find out if the resulting mutant will be more sensitive to oxidative stress. Another project involves the purification, cloning, and expression of the free- methionine sulfoxide reductase from E. coli. This protein is able to reduce free methionine sulfoxide exclusively. We hope to learn more about these two enzymes in order to understand their regulation and mechanism of action.
| Moskovitz, J; Poston, J M; Berlett, B S et al. (2000) Identification and characterization of a putative active site for peptide methionine sulfoxide reductase (MsrA) and its substrate stereospecificity. J Biol Chem 275:14167-72 |
| Moskovitz, J; Berlett, B S; Poston, J M et al. (1999) Methionine sulfoxide reductase in antioxidant defense. Methods Enzymol 300:239-44 |
