ABSTRACT
Iron-sulfur clusters are found throughout Biology as active sites of proteins [1-4]. As shown in Figure 1, they exist in a variety of forms-2Fe, 3Fe, 4Fe, and higher nuclearities-comprising bridging “inorganic” sulfides, usually (but not always) coordinated to the protein by the side-chain thiolates (RS−) of cysteine ligands, and very occasionally containing a metal other than Fe. These ligands often lie in a recognizable sequence of amino acids (the “binding motif”) that is characteristic of a particular cluster and enables its presence in a protein to be predicted from the gene. Iron-sulfur clusters function in a wide range of biological processes: Table I shows that aside from their longestablished place among electron-transfer centers, known roles (to the present century) include redox catalysis (nitrogenase), acid-base catalysis (e.g., aconitase), atom-transfer catalysis (biotin synthase), transcriptional regulation (e.g., the fumarate-nitrate regulatory protein FNR-a transcription factor that senses the oxygen tension in bacterial cells in order to switch between aerobic and anaerobic respiration), translational regulation (e.g., the “iron-regulatory protein” IRP that senses Fe levels to control Fe uptake and storage by eukaryotic cells), and oxygen-sensitive enzymatic regulation [1-11]. Aside from these activities, iron-sulfur clusters are important in stabilizing protein conformation, possibly serving a role like that of disulfide bridges or structural Zn sites. Special proteins coordinating clusters are also implicated in cluster biosynthesis [12]
