Spector Daniel, Etienne Frantzy, Brot Nathan, Weissbach Herbert
Center for Molecular Biology and Biotechnology, Florida Atlantic University, Boca Raton, FL 33431, USA.
Biochem Biophys Res Commun. 2003 Mar 7;302(2):284-9. doi: 10.1016/s0006-291x(03)00163-3.
It is known that reactive oxygen species can oxidize methionine residues in proteins in a non-stereospecific manner, and cells have mechanisms to reverse this damage. MsrA and MsrB are members of the methionine sulfoxide family of enzymes that specifically reduce the S and R forms, respectively, of methionine sulfoxide in proteins. However, in Escherichia coli the level of MsrB activity is very low which suggested that there may be other enzymes capable of reducing the R epimer of methionine sulfoxide in proteins. Employing a msrA/B double mutant, a new peptide methionine sulfoxide reductase activity has been found associated with membrane vesicles from E. coli. Both the R and S forms of N-acetylmethionine sulfoxide, D-ala-met(o)-enkephalin and methionine sulfoxide, are reduced by this membrane associated activity. The reaction requires NADPH and may explain, in part, how the R form of methionine sulfoxide in proteins is reduced in E. coli. In addition, a new soluble Msr activity was also detected in the soluble extracts of the double mutant that specifically reduces the S epimer of met(o) in proteins.
众所周知，活性氧能够以非立体特异性方式氧化蛋白质中的甲硫氨酸残基，而细胞具有逆转这种损伤的机制。MsrA和MsrB是甲硫氨酸亚砜酶家族的成员，它们分别特异性还原蛋白质中甲硫氨酸亚砜的S型和R型。然而，在大肠杆菌中，MsrB的活性水平非常低，这表明可能存在其他能够还原蛋白质中甲硫氨酸亚砜R型差向异构体的酶。利用msrA/B双突变体，发现了一种与大肠杆菌膜泡相关的新的肽甲硫氨酸亚砜还原酶活性。这种膜相关活性可还原N-乙酰甲硫氨酸亚砜、D-丙氨酰-甲硫氨酸（亚砜）-脑啡肽和甲硫氨酸亚砜的R型和S型。该反应需要NADPH，这可能部分解释了大肠杆菌中蛋白质中甲硫氨酸亚砜R型是如何被还原的。此外，在双突变体的可溶性提取物中还检测到一种新的可溶性Msr活性，它特异性还原蛋白质中蛋氨酸（亚砜）的S型差向异构体。
