Chapter 13 Glutaredoxin: The Missing Link Between Thiol-Disulfide Oxidoreductases and Iron Sulfur Enzymes

Abstract

The CXXC motif is present in many disulfide oxidoreductases as thioredoxins, glutaredoxins, and protein disulfide isomerases. It is also present in several metal-binding structures including hemoproteins and iron sulfur proteins. Although the 3D structure of ferredoxins and thioredoxins is radically different, the presence of this motif in both proteins suggests that thioredoxins and their derivatives might be able to accommodate iron sulfur centers (ISCs) as well. Several studies have indeed proven the presence of metals, such as iron or zinc, in thioredoxin-like structures either as natural products or after mutagenesis as in Escherichia coli thioredoxin 1. Moreover, it was recently demonstrated that some glutaredoxin species with CGYC or CGFS active sites can assemble a [2Fe–2S] ISC in a homodimer. Quite surprisingly, the ligands are the glutaredoxin catalytic cysteine and an external glutathione molecule. As a yeast CGFS glutaredoxin is thought to be involved in the transfer of preassembled ISCs from scaffold to acceptor apoproteins, this suggests that glutaredoxins are involved in these pathways through their own capacity to assemble such centers and transfer them efficiently. Altogether, these data provide firm evidence that glutaredoxins are a link between the world of thiol-disulfide reductases and iron sulfur enzymes.