Methionine Sulfoxide Reductase A (MSRA) is an enzyme that plays a crucial role in the repair of oxidative damage to proteins. This enzyme is responsible for the reduction of methionine sulfoxide (MetO) back to methionine, thereby restoring the normal function of oxidized proteins. The human recombinant form of MSRA is produced using recombinant DNA technology, which allows for the production of large quantities of the enzyme for research and therapeutic purposes.
MSRA is part of the methionine sulfoxide reductase (Msr) system, which consists of two families of enzymes: MsrA and MsrB. These enzymes are stereospecific, with MsrA reducing the S-form of MetO and MsrB reducing the R-form . The primary function of MSRA is to repair oxidative damage to proteins, which can occur under physiological and pathological conditions due to exposure to reactive oxygen species (ROS) and hydrogen peroxide .
The reduction of MetO by MSRA is essential for maintaining cellular function and protecting against oxidative stress. Oxidative stress can lead to the accumulation of MetO-modified proteins, which may alter their function or cause the accumulation of toxic proteins in cells . By reducing MetO to methionine, MSRA helps to prevent these detrimental effects and supports cellular homeostasis.
Human MSRA is expressed in various tissues, with the highest levels found in the kidney and nervous tissue . The enzyme’s activity is dependent on thioredoxin, a small protein that acts as an electron donor in the reduction process . The subcellular distribution of MSRA can be regulated by alternative splicing of its first exon, which affects its localization within the cell .
MSRA has been implicated in several physiological and pathological processes. For example, it has been shown to play a role in the activation of sulindac, a nonsteroidal anti-inflammatory prodrug, to its active metabolite sulindac sulfide . This activation occurs in human tissues and contributes to the drug’s therapeutic effects. Additionally, MSRA’s role in reducing oxidative damage makes it a potential target for therapeutic interventions aimed at mitigating oxidative stress-related diseases.