Glutaredoxin catalysis requires two distinct glutathione interaction sites

• DOI: 10.1038/ncomms14835
• Publication Date: 2017-04-04T12:57:18Z
• Authors: Patricia Begas; Linda Liedgens; Anna Moseler; Andreas J. Meyer; Marcel Deponte
• Keywords: Glutaredoxin

Abstract Glutaredoxins are key players in cellular redox homoeostasis and exert a variety of essential functions ranging from glutathione-dependent catalysis to iron metabolism. The exact structure–function relationships mechanistic differences among glutaredoxins that active or inactive standard enzyme assays have so far remained elusive despite numerous kinetic structural studies. Here, we elucidate the enzymatic mechanism showing require two distinct glutathione interaction sites for efficient catalysis. first site interacts with moiety glutathionylated disulfide substrates. second activates as reducing agent. We propose requirement reduction substrates explains deviating relationships, activities substrate preferences different glutaredoxin subfamilies well thioredoxins. Our model also provides crucial insights design optimization artificial glutaredoxins, transition-state inhibitors glutaredoxin-coupled sensors.