stabilize the 4Fe-4S cluster in the catalytic subunit. Structurally, the α subunit is very similar to the PsaE protein, a subunit of Photosystem I, though the similarity is not seen in their sequences or functions. The catalytic β subunit has a general α-helical structure with an [4Fe-4S center]. The FeS center and redox-active Cysteine residues are located within the loops of these helices. Cysteine-55, 74, 76, and 85 are coordinated to the iron atoms of the cubane-type cluster. Enzymatic Mechanism FTR is unique among thioredoxin reductases because it uses an Fe-S cluster cofactor rather than flavoproteins to reduce disulfide bonds. FTR catalysis begins with its interaction with reduced Ferredoxin. This proceeds with the attraction between FTR Lys-47 and Ferredoxin Glu-92. One electron from Ferredoxin and one electron from the Fe-S center is abstracted to break FTR's Cys-87 and Cys-57 disulfide bond, create a nucleophilic Cys-57, and oxidize the Fe-S center from [4Fe-4S]2+ to [4Fe-4S]3+. The structure of this one-electron (from Ferredoxin) intermediate is contested: Staples et al. suggest Cys-87 is coordinated to a Sulfur in the Fe-S center while Dai et al. argue Cys-87 is coordinated to an Iron. Next, the nucleophilic Cys-57, encouraged by an adjacent Histidine residue, attacks a disulfide bridge on Thioredoxin, creating a hetero-disulfide Thioredoxin intermediate. Lastly, a newly docked Ferredoxin molecule delivers the final electron to the FeS center, reducing it to its original 2+ state, reforming the Cys-87, Cys-57 disulfide, and fully reducing thioredoxin to two thiols. References External links Protein domains EC 1.8.7