Methionine residues may protect proteins from critical oxidative damage.
Cysteine and methionine are the two sulfur-containing residues normally found in proteins. Cysteine residues function in the catalytic cycle of many enzymes, and they form disulfide bonds which contribute to protein structure. In contrast, the key functions of methionine residues are not known. We propose that methionine residues constitute an important antioxidant defense mechanism. A variety of oxidants react readily with methionine to form methionine sulfoxide, and surface exposed methionine residues create an extremely high concentration of reactant, providing for efficient scavenging of oxidants. The effect of hydrogen peroxide exposure upon glutamine synthetase from Escherichia coli was studied as an in vitro model system. Eight of the sixteen methionine residues could be oxidized with little effect on activity. 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 sulfoxide can be reduced back to methionine by the enzyme methionine sulfoxide reductase, providing a catalytic amplification of the antioxidant potential of each methionine residue. Given the importance of oxidative stress during aging, the potential function of methionine residues as antioxidants during aging should be investigated experimentally.
Levine
R L
RL
Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-0320, USA. rlevine@nih.gov
Berlett
B S
BS
Moskovitz
J
J
Mosoni
L
L
Stadtman
E R
ER
D000975:Antioxidants / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism*; D051150:Methionine Sulfoxide Reductases; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*
D000975:Antioxidants; D016877:Oxidants; D011506:Proteins; D008715:Methionine; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; D010450:Endopeptidases; D005974:Glutamate-Ammonia Ligase; C013111:methionine sulfoxide