monothiolglutaredoxiner

Monothiol glutaredoxins, or CGFS-type glutaredoxins, are a family of small thiol-disulfide oxidoreductases characterized by an active-site sequence CGFS. They belong to the broader glutaredoxin family but differ from classic dithiol glutaredoxins, which carry a CXXC motif and use two catalytic cysteines. Monothiol Glrxs operate primarily through a glutathione-dependent mechanism that invokes a single catalytic cysteine to form mixed disulfides with substrates.

Structure and mechanism: They retain a thioredoxin-like fold and are typically around 10-15 kDa. The CGFS motif is essential for catalytic activity. In many organisms, monothiol Grxs participate in binding and handling iron-sulfur ([Fe-S]) clusters, forming holo complexes with glutathione and acting as carriers for Fe-S cluster delivery to recipient proteins.

Biological roles: The major established function is in iron-sulfur cluster biosynthesis and iron homeostasis. In mitochondria, CGFS-type Grxs such as GLRX5 bind [2Fe-2S] clusters in conjunction with GSH and participate in their assembly and transfer to apo-proteins. In yeast cytosol, Grx3 and Grx4 (CGFS-type) participate in iron regulation and redox signaling, often with BolA-like partners. Monothiol Grxs also contribute to the cellular redox buffering network and can mediate reversible protein S-glutathionylation.

Distribution and examples: Monothiol glutaredoxins are found in bacteria, yeast, plants, and animals. Notable examples include yeast Grx3 and Grx4, yeast Grx5 in mitochondria, and mammalian GLRX5. Their precise roles can vary by organism but share reliance on GSH and the CGFS active site to modulate thiol status and Fe-S chemistry.