Crystal structure of yeast monothiol glutaredoxin Grx6 in complex with a glutathione-coordinated [2Fe-2S] cluster

Glutaredoxins (Grxs) constitute a superfamily of proteins that perform diverse biological functions. The Saccharomyces cerevisiae glutaredoxin Grx6 not only serves as a glutathione (GSH)‐dependent oxidoreductase and as a GSH transferase, but also as an essential [2Fe–2S]‐binding protein. Here, the dimeric structure of the C‐terminal domain of Grx6 (holo Grx6C), bridged by one [2Fe–2S] cluster coordinated by the active‐site Cys136 and two external GSH molecules, is reported. Structural comparison combined with multiple‐sequence alignment demonstrated that holo Grx6C is similar to the [2Fe–2S] cluster‐incorporated dithiol Grxs, which share a highly conserved [2Fe–2S] cluster‐binding pattern and dimeric conformation that is distinct from the previously identified [2Fe–2S] cluster‐ligated monothiol Grxs. The dimeric structure of the C‐terminal domain of Grx6, bridged by one [2Fe–2S] cluster coordinated by the active‐site Cys136 and two external glutathione molecules, is reported.