Rosenfeld Mark A, Yurina Lyubov V, Vasilyeva Alexandra D
N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, 119334 Russia.
Biophys Rev. 2023 Apr 10;15(3):367-383. doi: 10.1007/s12551-023-01056-7. eCollection 2023 Jun.
Significant evidence suggests that reversible oxidation of methionine residues provides a mechanism capable of scavenging reactive species, thus creating a cycle with catalytic efficiency to counteract or mitigate deleterious effects of ROS on other functionally important amino acid residues. Because of the absence of MSRs in the blood plasma, oxidation of methionines in extracellular proteins is effectively irreversible and, therefore, the ability of methionines to serve as interceptors of oxidant molecules without impairment of the structure and function of plasma proteins is still debatable. This review presents data on the oxidative modification of both intracellular and extracellular proteins that differ drastically in their spatial structures and functions indicating that the proteins contain antioxidant methionines/the oxidation of which does not affect (or has a minor effect) on their functional properties. The functional consequences of methionine oxidation in proteins have been mainly identified from studies in vitro and, to a very limited extent, in vivo. Hence, much of the functioning of plasma proteins constantly subjected to oxidative stress remains unclear and requires further research to understand the evolutionary role of methionine oxidation in proteins for the maintenance of homeostasis and risk factors affecting the development of ROS-related pathologies. Data presented in this review contribute to increased evidence of antioxidant role of surface-exposed methionines and can be useful for understanding a possible mechanism that supports or impairs structure-function relationships of proteins subjected to oxidative stress.
大量证据表明,甲硫氨酸残基的可逆氧化提供了一种能够清除活性物质的机制,从而形成一个具有催化效率的循环,以抵消或减轻活性氧对其他功能重要的氨基酸残基的有害影响。由于血浆中不存在甲硫氨酸亚砜还原酶,细胞外蛋白质中甲硫氨酸的氧化实际上是不可逆的,因此,甲硫氨酸在不损害血浆蛋白质结构和功能的情况下作为氧化剂分子拦截剂的能力仍存在争议。本综述展示了关于细胞内和细胞外蛋白质氧化修饰的数据,这些蛋白质在空间结构和功能上有很大差异,表明这些蛋白质含有抗氧化甲硫氨酸,其氧化对它们的功能特性没有影响(或影响较小)。蛋白质中甲硫氨酸氧化的功能后果主要是通过体外研究确定的,在体内的研究非常有限。因此,血浆蛋白在持续氧化应激下的许多功能仍不清楚,需要进一步研究以了解甲硫氨酸氧化在蛋白质中对维持体内平衡的进化作用以及影响活性氧相关疾病发展的风险因素。本综述中呈现的数据有助于增加表面暴露的甲硫氨酸抗氧化作用的证据,并有助于理解支持或损害遭受氧化应激的蛋白质结构 - 功能关系的可能机制。