Stereospecific oxidation of calmodulin by methionine sulfoxide reductase A.

Stereospecific oxidation of calmodulin by methionine sulfoxide reductase A.
复制标题

蛋氨酸亚砜还原酶 A 立体定向氧化钙调蛋白。

DOI:
10.1016/j.freeradbiomed.2013.04.004
复制
发表时间:
2013-08
影响因子:
7.4
通讯作者:
Levine, Rodney L.
Levine, Rodney L.
中科院分区:
医学1区
文献类型:
--
作者:
Lim, Jung Chae;Kim, Geumsoo;Levine, Rodney L.

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甲硫氨酸亚砜还原酶A长期以来一直被认为可以还原游离氨基酸和蛋白质中的S-甲硫氨酸亚砜。最近,该酶被证明是双向的,能够将游离蛋氨酸和蛋白质中的蛋氨酸氧化为S-蛋氨酸亚砜。已经提出了一种控制方向性的可行机制,提高了蛋白质内甲硫氨酸残基的可逆氧化和还原是基于氧化还原的细胞调节机制的可能性。我们进行了研究,旨在确定蛋白质,是受位点特异性,立体特异性氧化和还原的甲硫氨酸残基。我们发现,钙调素,其中有9个蛋氨酸残基,是这样的甲硫氨酸亚砜还原酶A的底物。当钙调素处于其钙结合形式时,Met 77被甲硫氨酸亚砜还原酶A氧化为S-甲硫氨酸亚砜。当甲硫氨酸亚砜还原酶A在还原方向上操作时,氧化的钙调蛋白被完全还原回其天然形式。我们的结论是,可逆的共价修饰Met 77可以调节钙调素与一个或多个其许多目标的相互作用。
Methionine sulfoxide reductase A has long been known to reduce S-methionine sulfoxide, both as a free amino acid and within proteins. Recently the enzyme was shown to be bidirectional, capable of oxidizing free methionine and methionine in proteins to S-methionine sulfoxide. A feasible mechanism for controlling the directionality has been proposed, raising the possibility that reversible oxidation and reduction of methionine residues within proteins is a redox-based mechanism for cellular regulation. We undertook studies aimed at identifying proteins that are subject to site-specific, stereospecific oxidation and reduction of methionine residues. We found that calmodulin, which has 9 methionine residues, is such a substrate for methionine sulfoxide reductase A. When calmodulin is in its calcium bound form, Met77 is oxidized to S-methionine sulfoxide by methionine sulfoxide reductase A. When methionine sulfoxide reductase A operates in the reducing direction, the oxidized calmodulin is fully reduced back to its native form. We conclude that reversible covalent modification of Met77 may regulate the interaction of calmodulin with one or more of its many targets.
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