Zhang Xing-Hai, Weissbach Herbert
Department of Biological Sciences, Florida Atlantic University, Boca Raton 33431, USA.
Biol Rev Camb Philos Soc. 2008 Aug;83(3):249-57. doi: 10.1111/j.1469-185X.2008.00042.x.
The majority of extant life forms thrive in an O2-rich environment, which unavoidably induces the production of reactive oxygen species (ROS) during cellular activities. ROS readily oxidize methionine (Met) residues in proteins/peptides to form methionine sulphoxide [Met(O)] that can lead to impaired protein function. Two methionine sulphoxide reductases, MsrA and MsrB, catalyse the reduction of the S and R epimers, respectively, of Met(O) in proteins to Met. The Msr system has two known functions in protecting cells against oxidative damage. The first is to repair proteins that have lost activity due to Met oxidation and the second is to function as part of a scavenger system to remove ROS through the reversible oxidation/reduction of Met residues in proteins. Bacterial, plant and animal cells lacking MsrA are known to be more sensitive to oxidative stress. The Msr system is considered an important cellular defence mechanism to protect against oxidative stress and may be involved in ageing/senescence. MsrA is present in all known eukaryotes and eubacteria and a majority of archaea, reflecting its essential role in cellular life. MsrB is found in all eukaryotes and the majority of eubacteria and archaea but is absent in some eubacteria and archaea, which may imply a less important role of MsrB compared to MsrA. MsrA and MsrB share no sequence or structure homology, and therefore probably emerged as a result of independent evolutionary events. The fact that some archaea lack msr genes raises the question of how these archaea cope with oxidative damage to proteins and consequently of the significance of msr evolution in oxic eukaryotes dealing with oxidative stress. Our best hypothesis is that the presence of ROS-destroying enzymes such as peroxiredoxins and a lower dissolved O2 concentration in those msr-lacking organisms grown at high temperatures might account for the successful survival of these organisms under oxidative stress.
大多数现存的生命形式在富含氧气的环境中茁壮成长，而这不可避免地会在细胞活动过程中诱导活性氧（ROS）的产生。ROS很容易将蛋白质/肽中的甲硫氨酸（Met）残基氧化，形成甲硫氨酸亚砜[Met(O)]，这可能导致蛋白质功能受损。两种甲硫氨酸亚砜还原酶，MsrA和MsrB，分别催化蛋白质中Met(O)的S型和R型差向异构体还原为Met。Msr系统在保护细胞免受氧化损伤方面有两个已知功能。第一个功能是修复因Met氧化而失去活性的蛋白质，第二个功能是作为清除系统的一部分，通过蛋白质中Met残基的可逆氧化/还原作用来清除ROS。已知缺乏MsrA的细菌、植物和动物细胞对氧化应激更敏感。Msr系统被认为是一种重要的细胞防御机制，可抵御氧化应激，并且可能与衰老/老化有关。MsrA存在于所有已知的真核生物、真细菌以及大多数古细菌中，这反映了它在细胞生命中的重要作用。MsrB存在于所有真核生物以及大多数真细菌和古细菌中，但在一些真细菌和古细菌中不存在，这可能意味着MsrB与MsrA相比作用不那么重要。MsrA和MsrB没有序列或结构同源性，因此可能是独立进化事件的结果。一些古细菌缺乏msr基因这一事实引发了一个问题，即这些古细菌如何应对蛋白质的氧化损伤，进而引发了msr进化在有氧真核生物应对氧化应激中的意义的问题。我们最好的假设是，在高温下生长的那些缺乏msr的生物体中，存在诸如过氧化物酶等ROS破坏酶以及较低的溶解氧浓度，这可能是这些生物体在氧化应激下成功存活的原因。
