Histidine Ligated Iron-Sulfur Peptides.

Area of Science:

• Biochemistry
• Astrobiology
• Origin of Life Studies

Background:

• Iron-sulfur clusters are ancient cofactors potentially vital for early metabolic systems.
• Historically, plausible iron-sulfur clusters required cysteine ligands, but some modern proteins use histidine.
• This study explores alternative ligation modes for iron-sulfur clusters.

Purpose of the Study:

• To investigate if cysteine- and histidine-containing peptides can coordinate mononuclear Fe2+ and [2Fe-2S] clusters.
• To compare the properties of these peptide-metal complexes with purified iron-sulfur proteins.
• To assess the prebiotic plausibility and potential role of such complexes in early life.

Main Methods:

• Coordination of Fe2+ and [2Fe-2S] clusters by small peptides (≤6 amino acids) containing cysteine and histidine.
• Characterization using UV-vis, circular dichroism, and paramagnetic NMR spectroscopies.
• Electrochemical analysis via cyclic voltammetry.

Main Results:

• Small peptides successfully coordinated [2Fe-2S] clusters using a mix of cysteine and histidine residues.
• The reduction potentials of these peptide-cluster complexes were comparable to those of corresponding proteins.
• Demonstrated the ability of simple peptides to form functional iron-sulfur complexes.

Conclusions:

• Cysteine and histidine residues in small peptides can effectively ligate [2Fe-2S] clusters.
• These findings support the hypothesis that simple peptide-metal complexes were important in early cell-like systems.
• Suggests a broader range of ligands may have been involved in early iron-sulfur cluster biochemistry.