METHIONINE RESIDUES AS ENDOGENOUS ANTIOXIDANTS IN PROTEINS

Cysteine and methionine are tile two sulfur-containing residues normal ly found in proteins, Cysteine residues function in the catalytic cycl e of many enzymes, and they can form disulfide bonds that contribute t o protein structure. In contrast, the specific functions of methionine residues are not known. We propose that methionine residues constitut e an important antioxidant defense mechanism, A variety of oxidants re act readily with methionine to farm methionine sulfoxide, and surface exposed methionine residues create an extremely high concentration of reactant, available as an efficient oxidant scavenger, Reduction back Po methionine by methionine sulfoxide reductases would allow the antio xidant system to function catalytically. The effect of hydrogen peroxi de exposure upon glutamine synthetase from Escherichia coli was studie d as an in vitro model system, Eight of the 16 methionine residues cou ld he oxidized with little effect on catalytic activity of the enzyme, The oxidizable methionine residues were found to be relatively surfac e exposed, whereas the intact residues were generally buried within th e core of the protein. Furthermore, the susceptible residues were phys ically arranged in an array that guarded the entrance to the active si te.