Histidine ligated Iron-Sulfur Proteins and Peptides

Iron-sulfur clusters play a fundamental role in biology and are believed 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 been obtained through cysteine coordination to the iron ions. 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. In this thesis, we investigated the ability of cysteine- and histidine-containing proteins and peptides to coordinate mononuclear [1Fe-0S] centers and a [2Fe-2S] clusters. 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.