Methionine residues as endogenous antioxidants in proteins.
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 can form disulfide bonds that contribute to protein structure. In contrast, the specific 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, available as an efficient oxidant scavenger. Reduction back to methionine by methionine sulfoxide reductases would allow the antioxidant system to function catalytically. The effect of hydrogen peroxide exposure upon glutamine synthetase from Escherichia coli was studied as an in vitro model system. Eight of the 16 methionine residues could be oxidized with little effect on catalytic activity of the enzyme. The oxidizable methionine residues were found to be relatively surface exposed, whereas the intact residues were generally buried within the core of the protein. Furthermore, the susceptible residues were physically arranged in an array that guarded the entrance to the active site.
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
Mosoni
L
L
Berlett
B S
BS
Stadtman
E R
ER
D000595:Amino Acid Sequence; D000975:Antioxidants; D001665:Binding Sites; D003198:Computer Simulation; D003545:Cysteine; D004795:Enzyme Stability; D004926:Escherichia coli / Q000201:enzymology; D005974:Glutamate-Ammonia Ligase / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D006861:Hydrogen Peroxide; D008715:Methionine; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D011487:Protein Conformation; D012984:Software
D000975:Antioxidants; D010446:Peptide Fragments; D008715:Methionine; D006861:Hydrogen Peroxide; D005974:Glutamate-Ammonia Ligase; D003545:Cysteine