Thioredoxin disulfide loop

The pKa assignments, which have been controversial, are discussed in Chapter 7. This disulfide loop is reduced by NADPH through the action of the flavoprotein enzyme thioredoxin reductase. 

However, the two proteins have significantly different specificities and functions. The disulfide loop in glutaredoxin, whose eukaryotic forms are often called thioltransferases/ has the sequence CPYC. Although glutaredoxins are weaker reductants of mixed disulfides of proteins with glutathione than are thioredoxins/1 sthey are more specific. 

A variation is observed for E. coli thioredoxin reductase. The reducible disulfide and the NADPH binding site are both on the same side of the flavin rather than on opposite sides as in Fig. 15-12.190/259 Mercuric reductase also uses NADPH as the reductant transferring the 4S hydrogen. The Hg2+ presumably binds to a sulfur atom of the reduced disulfide loop and there undergoes reduction. The observed geometry of the active site is correct for this mechanism. 

The reaction catalyzed by the first of these is illustrated in Table 15-2 (reaction type F). The other two enzymes usually promote the reverse type of reaction, the reduction of a disulfide to two SH groups by NADPH (Eq. 15-22). Glutathione reductase splits its substrate into two halves while reduction of the small 12-kDa protein thioredoxin (Box 15-C) simply opens a loop in its peptide chain. The reduction of lipoic acid opens the small disulfide-containing 5-membered ring in that molecule. Each of these flavoproteins also contains within its structure a reducible disulfide group that participates in catalysis. 

Thus thioredoxin reductase, like its substrate thioredoxin, contains only two amino acid residues between the two half cystine residues and in both proteins the disulfide defines a small loop of only 14 atoms. 

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