The Oxidized Protein Repair Enzymes Methionine Sulfoxide Reductases and Their Roles in Protecting against Oxidative Stress, in Ageing and in Regulating Protein Function

Sofia Lourenço Dos Santos,Isabelle Petropoulos,Bertrand Friguet

doi:10.3390/antiox7120191

Abstract

Cysteine and methionine residues are the amino acids most sensitive to oxidation by reactive oxygen species. However, in contrast to other amino acids, certain cysteine and methionine oxidation products can be reduced within proteins by dedicated enzymatic repair systems. Oxidation of cysteine first results in either the formation of a disulfide bridge or a sulfenic acid. Sulfenic acid can be converted to disulfide or sulfenamide or further oxidized to sulfinic acid. Disulfide can be easily reversed by different enzymatic systems such as the thioredoxin/thioredoxin reductase and the glutaredoxin/glutathione/glutathione reductase systems. Methionine side chains can also be oxidized by reactive oxygen species. Methionine oxidation, by the addition of an extra oxygen atom, leads to the generation of methionine sulfoxide. Enzymatically catalyzed reduction of methionine sulfoxide is achieved by either methionine sulfoxide reductase A or methionine sulfoxide reductase B, also referred as to the methionine sulfoxide reductases system. This oxidized protein repair system is further described in this review article in terms of its discovery and biologically relevant characteristics, and its important physiological roles in protecting against oxidative stress, in ageing and in regulating protein function.

Highlights

Repair of protein oxidative damage is only possible for certain oxidation products of the sulfur-containing amino acids, cysteine and methionine
The rate of the recycling process by the Grx system is at particular case of A. thaliana MsrB1, the sulfenic acid is reduced by glutathione forming a least 10 to 100-fold lower compared to Trx acting in Methionine sulfoxide reductase (Msr) with a recycling cysteine, suggesting that the glutathionylated intermediate that is attacked by glutaredoxins [76]
We have tentatively provided a comprehensive review of the Msr system in terms of its discovery and biologically relevant characteristics as its important physiological roles in protecting against oxidative stress, in ageing and in regulating protein function

Summary

Introduction

Repair of protein oxidative damage is only possible for certain oxidation products of the sulfur-containing amino acids, cysteine and methionine. Thioredoxins (Trx) are small ubiquitous proteins with two catalytic redox active cysteines (Cys-XX-Cys), which catalyze the reversible reduction of protein disulfide bonds. Trx are thiol-dependent peroxidases (Prx), allowing the recycling of these Prx enzymes for the continuous involved in the protection against protein oxidative damages by reducing methionine sulfoxide removal of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Trx are reductases (Msrs), enzymes capable of repairing oxidized methionines. Trx involved in the protection against protein oxidative damages by reducing methionine sulfoxide regulates the activity of many redox‐sensitive transcription factors, such as NF‐κB, Nrf and p53 [1]. An exception was observed with the Grx reduction of disulfides and the participation on protein deglutathionylation state the importance of isoenzyme, which was shown to be reduced by Trx in mitochondria [4]. These proteins as well as their functions are further described and discussed

Methionine Sulfoxide Reductases Discovery

Methionine

Findings

Conclusions