Thioredoxin-like oxidoreductase

A highly thermostable protein disulfide oxidoreductase was first isolated from Sulfolobus solfataricus. From its ability to catalyze the reduction of insulin disulfides in the presence of dithiothreitol (DTT), the protein was considered a thioredoxin. The protein showed an unusually high molecular mass of 25 kDa and from amino acid composition analysis contained four cysteine residues. A homologous protein was subsequently purified from Pyrococcus furiosus. From its amino acid sequence, which showed two distinct CXXC motifs, and from its thioltransferase activity the protein was considered to be a glutaredoxin-like protein. 

Unlike thioredoxin, glutaredoxin, and DsbA, which possess only one thiore-doxin-like motif, P/PDO is the first protein disulfide oxidoreductase whose three-dimensional structure has been shown to contain two thioredoxin fold motifs with two active sites. Thus, P/PDO shows structural resemblance to PDI and PDI-like protein s. This structural feature suggests that P/PDO is probably not just a simple protein disulfide reductant like thioredoxin as described previously. It may belong to the growing family of PDI-like proteins. From a structural point of view, P/PDO may represent the simplest form of PDI. 

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