Alternative FeS cluster ligands: tuning redox potentials and chemistry

A subset of biological Fe-S clusters contain protein-based ligands other than cysteine (Cys). The most common alternative ligand is histidine, while aspartate, arginine, and threonine ligation have also been identified. With the exception of the 2-Cys, 2-His ligated Rieske clusters, the functions of these uniquely ligated clusters are, in general, poorly understood. Recent functional studies of a set of 3-Cys, 1-His ligated [2Fe-2S] clusters have begun to highlight the importance of non-Cys ligation in controlling both the redox and chemical properties of these clusters as well as their physiological stability. Here, a survey of non-Cys ligation motifs is examined along with the possible biological roles of these clusters.