ROLE OF METHIONINE RESIDUES IN ENZYME REGULATION

本实验室早期的研究证实，蛋白质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（R0S）的损伤。观察结果表明，蛋白质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：(a)一些酶的蛋氨酸残基的ros依赖氧化为蛋氨酸亚砜[Met(0)]导致活性丧失；(b)这些被氧化的酶的活性可以通过肽蛋氨酸亚砜还原酶（MSR）的作用，通过硫氧还蛋白依赖的将Met(0)还原回蛋氨酸来恢复。如果蛋氨酸残基的循环氧化还原是细胞调节的一种手段，细胞应该含有特定的氧化酶，可以选择性地氧化调节酶的蛋氨酸残基。我们已经开始了一项以磷酸果糖激酶和钙调蛋白为潜在靶点的研究，因为这些蛋白的活性会因独特的蛋氨酸残基的氧化或取代而严重改变。

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.