Methionine residues may protect proteins from critical oxidative damage

Cysteine and methionine are the two sulfur-containing residues normally fou nd in proteins. Cysteine residues function in the catalytic cycle of many e nzymes, and they form disulfide bonds which contribute to protein structure . In contrast: the key functions of methionine residues are not known. We p ropose that methionine residues constitute an important antioxidant defense mechanism. A variety of oxidants react readily with methionine to form met hionine sulfoxide, and surface exposed methionine residues create an extrem ely high concentration of reactant, providing for efficient scavenging of o xidants. The effect of hydrogen peroxide exposure upon glutamine synthetase from Escherichia coil was studied as an in vitro model system. Eight of th e sixteen methionine residues could be oxidized with little effect on activ ity. The oxidizable methionine residues were found to be relatively surface exposed while the intact residues were generally buried within the core of the protein. Further, the susceptible residues were physically arranged in an array which guarded the entrance to the active site. Methionine sulfoxi de can be reduced back to methionine by the enzyme methionine sulfoxide red uctase, providing a catalytic amplification of the antioxidant potential of each methionine residue. Given the importance of oxidative stress during a ging, the potential function of methionine residues as antioxidants during aging should be investigated experimentally. Published by Elsevier Science Ireland Ltd.