ROLE OF METHIONINE RESIDUES IN ENZYME REGULATION

该实验室早期的研究证实，蛋白质中蛋氨酸残基的循环氧化还原可以起到抗氧化作用，保护细胞免受活性氧物种(ROS)的损害。蛋白质中蛋氨酸残基的循环氧化还原也可能在某些酶的活性调节中起重要作用。观察结果表明：(A)某些酶的蛋氨酸残基依赖ROS氧化为蛋氨酸亚砜[Met(0)]导致活性丧失；(B)这种被氧化的酶的活性可以通过硫氧还蛋白依赖的Met(0)还原为蛋氨酸来恢复。如果蛋氨酸残基的循环氧化-还原是一种细胞调节手段，细胞应该含有特定的氧化酶，它可以选择性地氧化调节酶的蛋氨酸残基。我们已经启动了一项研究，以磷酸果糖激酶和钙调蛋白为潜在靶点来寻找这类酶，因为这些蛋白质的活性会被氧化或取代独特的蛋氨酸残基而严重改变。

Earlier studies in this laboratory established that the cyclic oxidation-reduction of methionine residues of proteins can serve an antioxidant function to protect cells from damage by reactive oxygen species (R0S). The possibility that cyclic oxidation-reduction of methionine residues of proteins may also play an important role in the regulation of some enzyme activities is suggested by the observations: (a) The ROS-dependent oxidation of methionine residues of some enzymes to methionine sulfoxide [Met(0)] leads to loss of activity and (b) activity of such oxidized enzymes can be restored by the thioredoxin-dependent reduction of the Met(0) back to methionine by the action of peptide methionine sulfoxide reductase (MSR). If the cyclic oxidation-reduction of methionine residues is a means of cellular regulation, cells should contain specific oxidases that can selectively oxidize methionine residues of the regulatory enzymes. We have initiated a study to search for such enzymes using phosphofructokinase and calmodulin as potential targets, since the activities of these proteins are severely altered by oxidation or substitutions of unique methionine residues.