Iron–Sulfur Proteins

Abstract Iron–sulfur proteins contain iron coordinated by at least one sulfur ligand and include proteins with mononuclear Fe centers with partial or complete cysteinyl sulfur ligation as well as proteins containing clusters of iron and inorganic sulfide. This review summarizes the structural, electronic, and redox properties of protein‐bound mononuclear FeS centers and FeS clusters containing [2Fe2S], [3Fe4S], and [4Fe4S] cores. In addition to the ubiquitous role in mediating biological electron transport, the roles of FeS centers have proliferated to include coupling of electron and proton transfer, substrate binding and activation, determining protein structure, regulation of gene expression and enzymatic activity, disulfide reduction, and iron, electron, or cluster storage. The diverse roles of FeS clusters are illustrated by discussion of specific systems: the mitochondrial and photosynthetic electron transport chains and a wide range of soluble redox enzymes and proteins; the active sites of nitrile hydratase, aconitase‐type (de)hydratases, superoxide reductase (SOR), radical‐SAM (S‐adenosylmethionine) enzymes, NiFe‐ and Fe‐hydrogenase, sulfite and nitrite reductase, nitrogenase, CO dehydrogenase, and acetyl‐CoA synthase; the structural FeS centers in DNA repair enzymes; the regulatory roles of FeS centers in the SoxR, fumarate–nitrate reduction (FNR), IscR/SufR, and iron‐regulatory protein (IRP) proteins and in selected enzymes; the two classes of FeS cluster containing disulfide reductases typified by ferredoxin–thioredoxin reductase (FTR) and heterodisulfide reductase (HDR); and the role of 8Fe ferredoxins and polyferredoxins in iron, electron, or cluster storage.