Summary
Redox-active thiols play a major role in the mechanisms of essential biosynthetic and repair enzymes, defense against oxidative stress or thiol redox control of transcription, translation and enzyme activity. Thioredoxins are strong reductants having a dithiol in the conserved active site sequence: Cys-Gly-Pro-Cys which is essential for catalytic activity in disulfide reduction. Thioredoxin reductase regenerates the dithiol form of thioredoxin with electrons from NADPH. Unique to photosynthesis, chloroplasts have ferredoxin-thioredoxin reductase, which reduces target specific thioredoxins f and m by electrons from light to control the activity of CO2 assimilation enzymes. The other major disulfide reducing system is comprised of glutaredoxins, glutathione and glutathione reductase which together catalyze disulfide reductions by NADPH, either in dithiol reactions with functions overlapping that of thioredoxins, or unique in monothiol reactions. In this way, changes in the redox potential of the cellular redox buffer of glutathione and its disulfide can be transmitted for reversible regulation of protein function by thiol redox control. The thioredoxin superfamily of proteins comprise thioredoxins, glutaredoxins, glutathione peroxidases, thioredoxin peroxidases, glutathione transferases or protein disulfide isomerases all of which encompass the thioredoxin fold, a three-dimensional structure with a βαβαββα unit and a unique cis-proline residue.
Recent studies on three-dimensional structures of ferredoxin-thioredoxin reductase and target enzymes, such as malatede hydrogenase and fructose bisphosphatase having unique extensions with regulatory disulfides, have greatly advanced the knowledge about redox signaling systems unique to plants. Plants have unusually many thioredoxin and glutaredoxin genes with as yet incompletely known functions. Remarkably, plants have retained the low molecular weight type of thioredoxin reductase found in Archae, eubacteria and fungi. In contrast, Caenorhabditis elegans and mammalian thioredoxin reductases are selenocysteine-dependent enzymes of higher molecular weight with different mechanism and many additional functions. An exciting emerging field concerns redox regulation of transcription and translation via members of the thioredoxin superfamily.