Histidine Ligated Iron‐Sulfur Peptides

Iron‐sulfur clusters are thought to be ancient cofactors that could have played a role in early protometabolic systems. Thus far, redox active, prebiotically plausible iron‐sulfur clusters have always contained cysteine ligands to the cluster. However, extant iron‐sulfur proteins can be found to exploit other modes of binding, including ligation by histidine residues, as seen with [2Fe‐2S] Rieske and MitoNEET proteins. Here, we investigated the ability of cysteine‐ and histidine‐containing peptides to coordinate a mononuclear Fe(2+) center and a [2Fe‐2S] cluster and compare their properties with purified iron‐sulfur proteins. The iron‐sulfur peptides were characterized by UV‐vis, circular dichroism, and paramagnetic NMR spectroscopies and cyclic voltammetry. Small (≤6 amino acids) peptides can coordinate [2Fe‐2S] clusters through a combination of cysteine and histidine residues with similar reduction potentials as their corresponding proteins. Such complexes may have been important for early cell‐like systems.